Construction that Genome inconstancy is on limitting the virus with Capsid hepatitis
Grup virus Ent è rics, microbiology department university for, 巴赛隆纳 ,08028 巴赛隆纳 , Spaino+!q&, 百拇医药
Received the 2002 June 17/ the 2002 of the general acknowledgement September 24o+!q&, 百拇医药
KsIs alike to the poliovirus( PV) with the foot-and-mouth disease virus( FMDV), Ka is what size of 1 order of sequence ratio is lower. ThatNcThe parameter offering closes the information codon method of using of the 於～ the prejudice with reduce when prejudice gain. NcThe value is roughly in the HAV 38, idle away in the PV and the FMDV, it is roughly 53. 22 The emergence of the rare codons is in the front 8 moderate in the PV 7 in the FMDV disheveled hair now. Big part that keep of the strategy of rare codons P1 district the 於 that carboxy the edgeß Bucket with{alpha}o+!q&, 百拇医药
382325Inconstancy that the foundation of that numerator this inherit the gene and may be a high mistake 82325 滤 over the ratio RNA that sex poison the 菌 's RNA- suffer to bring up the polymerase correct the mechanism with nonattendance.Although have no a data to exsits on the mistake rate the HAV polymerase, variety frequency is a scope of various different RNA viruses from the each foundation replacement of each bout that 10-4 to 10-5 copy.(9)9The 9 什麽 that sour different race of nucleic of that persuasion is a sour different race does not match to contain the ammonia 基 to should rely on the lacking of nonsynonymous the variety, possiblely adequacy is to their obviation of negative choice.However, 聚 that the variety of delivering the true mold 态 , often is polluteding to unite, may lead to there to accumulating of that little tiny HAV population that food make person's crack-up.(7) 7 In the context, the low degree that that is refreshing contain the ammonia 7 基 sour in the ～ 's changes capsid the district suggest the strong construction restrict.
The current work, we began an analysis of the 核甘 And contain what ammonia 基 of sour in the ～ 's changes preface row performance that can get Strain is from the GenBank and from the insulation of a hepatitis of rare food A break out. Protein(4), the construction's model is a VP2, VP3, VP1 with 3 D The data that protein is from the reality inferences to is structural for that Poliovirus protein(13) with the foot-and-mouth disease virus (1) and from the reality of that poliovirus 3 D polymerase(12).j3y0, http://www.100md.com
Virus. Can get to GenBank of 15 complete of HAV preface the row is used in this research everywhere.These preface the row express a group of geographies of and at that time of the different HAV is tired( table1). additional,18 sharp hepatitis of strains at an a kind of consumption for break outing the inside from the patient quilt insulating the quilt coquina unite a clam.(24) 241 24 µL 浆 liquid the 抽 take the sample by the guanidine at elsewhere according to the description's thiocyanate treatment.(5,24) 524 524j3y0, http://www.100md.com
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Table 1. Complete of HAV preface row Can get at the GenBank with now use the researchue, http://www.100md.com
RT- The PCR enlarges with the 核甘 preface row. The P1-2 that that is complete the HAVs preface row insulate to is acquired at their after extend of because of thatPwo Transcribing of reverse side-( RT) PCR system( Roche) by follow behind to make the specification of the operator and because the handbook match the capsid protein genomic the district( table2). The RT of two directions- The PCR product preface row uses a Thermo Sequenase 2 2 颜料 terminator the period quilt circulate the preface row the premix by follow behind the material( the Amersham Pharmacia living the 化 technology) that manufacturing the operator's instruction with because of the ABI prism 377 in proper order 器 of automation DNA.( Perkin- elm)ue, http://www.100md.com
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Table 2. Handbook that used is with the circumstance because of the RT- The PCR enlarges with the HAV preface rowue, http://www.100md.com
核甘 with contain the analysis of the sour preface row of the ammonia 基 . The preface row that aim at the variety uses the ClustalW execution 19Plan by the DnaSP 19 ( 巴赛隆 the 纳 's university).
The in order to produces the codon method of using the table, poliovirus serotype for HAV 1 ( PV-1), with the foot-and-mouth disease virus serotype C,( FMDV- C) The sharp end plans( Europe of the molecular biology open the software suit) Were used.A the rare codon were defined to a the whose frequency is Little 於 30% that is in the most abundant synonym that it does ever had of the each inside that Codon method of using table(11). (Nc) measure the codon prejudice(26). ThatNc The value is always at 20( be the time that unique codon be used as availably each one to contain the ammonia 基 sour) And 61.( when the codons were aleatoricly use the timed) thatNc Plan by the 薯 ( the molecular biology of European open the software Suit).wp-&8, 百拇医药
Study to rare codon position of 於 , and the protein is inside the class's construction Electric wire details model that HAV VP2, VP3 is°which have project with VP1 From a the picornavirus aim at(16) true construction The data is nervous for PV-1 Mahoney Were increased and arrange. The three-dimensional space's model is that HAVprotomer too quilt Luo et al reasoning. (16; M. Luo, personal Communication) aim at from this. Statistics certain The position or allotment of that rare codons, a2 The frequency were take upped. The different protein is discrete Enter two districts inside: ( i) the carboxy end with the edge that is highly Construction 化 chemical element(ß Bucket with{alpha} The protein's surplus is part of. That so-called carboxy The extreme limit was is part for the third carboxied by definition that is structural Plus five close by exterior 残s stay the thing's chemical element. Instance, when thatß Bucket or that{alpha} Compare three 残s to stay the thing short, the remnant for having insidely is included; When compare five exteriors to attend there little of time the 残 stay the thing at Next the chemical element that is structural, total that attend the district Were included.If the short cut is worth a, contain rare codons conservancy At exceed 50% of the preface row inside is included in the ～ this research. At that2 Rare codons. PV-1 is with the FMDV- C true construction Capsid protein And), Recombinant HAV 3 C proteases true construction,() And HAV 3 D polymerases a models inference from the recombinant PV3D protein Used to the position's comparison analysis of that is rare Codons.
The value that logarithms( P- Num) have relation with ～ is different HM-175 genomic too the district that HAV is The nervous PV-1 were acquired from.4i, 百拇医药
核甘 preface the row arrive the number.P1-2 a 核甘 the18 preface row the insulation unite from that clam of Break out to is in the GenBank to deposit and have the quilt the allotment to arrive Arithmetic figureAF396391 AF396408.4i, 百拇医药
HAV of generally describe to insulate the hepatitis that unite from that clam on break outing. All 18 insulate to belong to the genotype IB, although 6 in the outside that 18 samples had to keep of contain the sour variety( Val arrive Ile) of the ammonia 基 in the remnant 72, in the VP3 preface the row's central inside, positive and participant in the immunodominant position.(24) 24This variety lures on losing the monoclonal antibody the antigenic K34C8 acknowledgement and like this expressing the occurrence to change. Two sour varieties that containing the ammonia 24 基 of affixtureses are disheveled hair now, in the VP2 position 40( to Ala Val at two strain) with the VP1 position 28.( run into the Val at the inside strain that a 核甘 ) that all are same alike to arrange in this 18 samples from 97.85 to 100% in the P1-2 an inside district, be to contain what ammonia the 基 's sour time same alike arrange from 99.75% to 100%s.
In the capsid frequency in the district is with the type variety. ThatKs AndKaIt is worth a to is°which have project to combination those second HAVs In the capsid preface in the district row( table3). Ks Value is Break out the preface row to is 7.5 times at the VP0 to with VP3 lower Low capsid district with 5 times are in the VP1-2 a district comparison that KsThe value is that GenBank preface row, when thatKa Value is 13.4,3, and 16 times lower, respectively.These consequently instructionses GenBank preface the row's cluster of high rift comparison Break out the preface row. ThatKs/Ka The ratio break outs the preface row for these Feel to kill is high to VP0 with the VP1-2 a district is with the immensely For the VP3 district high degree. The lower ratio of ratio observes for VP3 The district reflects what that relatively enrich(18 inside of 6 preface row) The antigenic change's occurrence in the top to describe. For that GenBank preface row, ratio right all is too very high That analyzed the genomic district. When complete of capsid district ( P1 district) HAV is with the FMDV-The C is compared, and generally discovers When thatKs The value is alike in two viruses, thatKa In the FMDV- C. The inside consequently is 1 order of sequence of high size is, that Ks/KaThe ratio is important high in the HAV( table3). While resembling of After conclusion is distressed in the value's a comparison for that HAV VP1 district, FMDV- C, with the PV-1( table3).
fig.ommitteed'ez, 百拇医药
Table 3. The variety's analysis at HAV preface row'ez, 百拇医药
Codon method of using. Later on is the most widespread from the synonym's variety to moderate the such variety occurrence to suffer the system 於 that influence codon the method of using in the HAV, in the method of using in the HAV an analysis take up.Complete of the beguilement genome study the preface row for GenBank quilt.10 5 included the synonym to emerge the usage of the rare codonsed from codons 18 sour family for containing the ammonia 基 ( table4). 4). 10 8 from these 20 rare codonses are row of similar to ～ that GenBank prefaceses of those, with 4 more( Arg:'ez, 百拇医药
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Table 4. Codons percentage because of Concern towards at HAV with mankind's cell codon inside the most abundant synonym Method of using table'ez, 百拇医药
NcWorth a, is 39 於s total amounts to cheat the district,38.8 for the capsid district, with 38.7 for the nonstructural district. ThatNcEvaluate the district for capsid at that break out the preface row is 38.9.These worth a designation that have no a codon method of using important and different prejudice at that in closely related break out the preface row with the GenBank preface row. ThatNcThe value also is computed for two others picornaviruses, PV-1 with FMDV- C( table5). Because of these two viruses, markedly compare higherNcThe worth a quilt acquires(52.6 with 52.1, respectively, for the HAV VP1 and 5 ～相 than 37.2;53.3 with 38.8 於s the P1FMDV of whole- C is with the HAV district, respectively), the designation HAV have a codon method of using high and a lot of prejudices. The further quilt of this fact confirms to be contained the ammonia 基 sour family of the arithmetic figure include rare codons or were compared by that clearly rare codons of high total amount is in the HAV compare in the another virus( table5). 5
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Table 5. Codon method of using is three picornaviruses1#, 百拇医药
4). for those three surplus of two times grounds deteriorate to contain the ammonia 基 sour, and the Lys, Gln may bind with Glu, each codon two tRNAs with unique anticodon quilt sharing; have no clarity of codon is partial to is shown by the HAV.For the codon triple deteriorate the Ile, the most abundant mankind to may bind two tRNAses, whose anticodons quilt sharing by two alternative plan codons; the second the most abundant codon may bind three anticodons( two sharing with an unshared); may bind with most without the abundant codon two anticodons.( penny enjoy and unshared)In this kind of situation, the codon HAV choice is such as the big part abundant to have an unshared codon anticodon and that are not rare to host cells. Same alike of the strategy were observed because of big part those four- And six times's depravities contain the ammonia 基 sour, although in some insides, for example the Val choose the rare and human codon with second monetary unit, HAV of Rome 尼 to consider as its enrich most of, have one's own the unshared other possible of codons hereafter the anticodon match most human codons that enrich, such competition of mightiness performance.
The position of the rare codons. The position of the rare codons is in the GenBank preface the row is inside is Study, although it is only the amount that codons consider the rare that Is current with rare at both all the GenBank moderate the hepatitis Break out the preface row( table4). Exceed 50% of analysis preface the row pass for the importance Reign to place the inside, and study.All,60 rare codonses be amounted by 764 The codons were kept in the P1 districts, and express 7.8% keep Rare codons.When urgently increase in the aegis To 85 or 100%,2.7 or 0.9%, respectively, total amount The P1 codons is a rare codons. It should notice that 7 in the outside This 60 rare codons(11.6%) quilts keep the group in whole Preface row.In some instances, the each one person that preface row is lacking Rare codon contain rare codon concluding the other that tie the possibility to near to ( a to three codonses distance), increase by the percentage aegis. Therefore,26 highly kepted the position should be very Turning point of were recognized out in the construction's genome.
The incline toing of ～ were located that in the carboxy extreme limit highly Constitute the chemical element(ß Bucket with{alpha} ( diagram1). All,52.7% of capsid district rare codons 於 carboxy extreme limit thatß Bucket And{alpha} 37.6% total polyprotein. The incline toing of ～ were located There importance for carboxy extreme limit statisticsing(P < 0.05). FMDV- C district with for the PV-1 VP1 district. An importance of Nonrandom position must not at too FMDV- The C inside is disheveled hair now or PV-1, although at both inside the virus is partial to to carboxy The extreme limit also is observed.:&ask1, 百拇医药
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Figure 1. The construction's VP2, VP3 is with the VP1 Electric wire details the model is a PV-1 from the data reasoning that true. (Mahoney):&ask1, 百拇医药
1). ßThe D quickly go forwardses, with the third along short attended to prolong the of row at that of all prefacesßF and thatßThe G1 quickly go forwardses.In the VP3 district, a the gathering is disheveled hair to only start now at that beforeßG2 bucket end for with in the construction's 後 only. In the VP1 district, a group of containing of 於 protein the terminal point of the ammonia 基 , with two time for drive locating at ～ ending thatßE bucket with at attend the preface row the of person at thatßE bucket with that{alpha} The B is spiral.Break out the preface row to not is included to arrive to avoid to be make sured by the latent prejudice of their be over of 於 relate to; however, their habit the position of the esse turning point in this analysis( diagram1). 1
Allly were changed to containing of secret code the ammonia 基 by these sour to all is located In the revelation capsid district( diagram2), and these come together Include very rare codons. Frequency these are very rare The codons is that their the most usual codon under 20% Family or even under 5% in some instances, for example that ThatßG2VP3 cluster.It should be recorded that not The codons for having first cluster besides outside some ones are rare also change to secret code The 残 of locating stays the thing at that on surface. All,67% of all are rare The codons changed to secret code the 残 to stay the thing in the capsid to superficially expose, more Accurate of,81,72, and 64% of VP2, VP3 is with the rare codons of VP1, Respectively. On the other hand,60% these rare codons is Highly keep at at least 85% GenBank preface row.$, 百拇医药
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Figure 2. Capsid surface position Were changed to containing of secret code the ammonia 基 by rare codons keeping sour in the HAV protomer Refinement model. ( Luo, individual communication) grillage, pink, with 蓝色 that the orb that 残 instructions VP2, VP3 stay the thing with the VP1, Respectively, the rare codons of quilt change to secret code. The yellow orb matches Arrive the 残 to stay the thing in the antigenic position to produce the relation.
The RNA composing of the inside class. Although the development's kind that RNA the genome avoid an exactitude of The prediction, P of the construction of its inside class-The Num is worth a to provide The tendency's quantity judges a then arrive the double make the foundation Together break the layer in suboptimal a collections with the partner of possibility other (20). RNA district with ～ contain abundant foundation low P- Num value (P-Num,<100) Were predicted the second construction of containment (20). This parameter has to plan any for the total genome HM-175, HAV strain or for the part's RNA district. Although There is P-The Num foundation percentage is worth a<100 Is 24.15%, The style quilt of a clarity observes at in different genomic District( table6). There is low P- The Num foundation value were observed in the P3 districts More moderate even to compare in the noncoding district in the P1 district, Tight construction of proposal is in that P3 district. Ratio In the different district P-Of the Num value is°which have project Because HAV is with the PV-1.P3 district/ P1 the district compare is 2.3 with 1.7, respectively, P3 district/5' noncoding district ratio Is 1.6 with 1.7, respectively, with the P1 district/5' noncoding The district compares is 0.7 with 1, respectively.These compare to suggest RNA that HAV P1 the district reach on comparatively comparing lower P- Num value with right should of a relatively looser composing.
fig.ommitteed6)4|, 百拇医药
Table 6. Validity ofNc6)4|, 百拇医药
14However, the antigenic change to have to is for them to choose to different MAbs of resisting of ～ .(18,21)1821At that in unite from the clam of break out to insulate, a the natural antigenic change to have disheveled hair now which lure the MAb K34C8 with the on-line epitope VP1 of a loss of the acknowledgement of a kind of the second variety.(24) 24However, the nonsynonymous frequency change to observe to compare those in the HAV importance of low picornaviruses is discovereds in others, for example PV-1 with FMDV. All, on place( remnant 5) in the VP4ing, four positions are in the VP2, in the VP3 of nine position( the 1821 24 残 stay the thing 25,28,148,156,174,208,216,241, with 271) that six position( the 残 stay the thing 32,45,72,92,145, with 239), with perform the inconstancy at the GenBank with break out the preface row the inside in the VP1. 1015 With the position 72 VP3.(18,21,24) 182124Additional, preface row that VP1 position 174 were located at come from the 1015 182124 残 to stay the thing 171 central to 176 the immunodominant position of this proteins, HAV of partially is which, although have no a data to epitope in containing of this position 意 on esse construction.(18,21) 1821Same alike of the situation apply the 1821 於残 to stay the thing 148,156, VP3 of and VP1 is with the remnant 145 inside of 241, is located in the partial 残 that the ～ that neighborhood is a HAV immunodominant position stay the thing in the HAV model of construction inside(16; Luo,16The individual's communication). in addition, the 16 残 stay the thing 208 with the VP1 inside of 216 in the ～ of nearby is located the remnant 221, define HAV a the second antigenic the position.(18,21) 182124 Then the extensive replacement that it can be expected that more right emergence is essential a the new serotype is with the replacement that that such to were is is sturdylied by bar structural restrict. 1821 24
The idea of general restrict of the strong capsid construction possibility Is a lot of usages of the rare codonses of quilts with protect to enhance, The whose strategy position contain quilt to request to produce the codon Context variety along mRNA, respond the ～ 's decrease translation Accelerate with the admission appropriate of protein fold of. ThatNc The value acquires Instructions to different picornaviruses of 於 a the importance's comparison highland Prejudice is in the codon method of using the aspect compare in the PV-1 or FMDV in the HAV- C. Gene inside because of The ratio is lowerNc The synonym's codons compares the highland to use the ～ and ～相 than geneNc Value, Have in the comparison in the usage that synonym that codons is very stick of 柔 (26). It may were supposed that low pointNc The value suggests usages to like better Codons and, result, the esse of the rare codons. Does the codon method of using designation is a synonym and may side with direction The part links the realm to is inside with the rare codons of the old customer the classes of Construction area segment(2,11). The rare codons of nonrandom allotment can be observed at that Capsid district, were ended by true carboxy of position like bettering And edge that highly constitute the protein chemical element. In the difference, Incline to not have the quilt to observe at 3 C region or flat At 3 in the D region, full of at 100% kept the rare codons Compare the P1 district. However, by the usage P- Num value that HM-175 strains is observed for the HAV, it such as the reference that for 3 constructions that D regions, RNA is inside classes are tight; result, Row of its preface should to ～ is not more couchant inconstancy, consider as is For the other virus proposal(11). 3 10 percentage with 64% of P1 district with 3 rare codons of D regions, respectively, is Use the low P- The Num value immerses in the RNA districts.( the data does not show) The result, it may be these rare codons games that considereds A dual role is all with protein in the maintenance RNA aspect construction, In the protein in the P1 level more important district with At the RNA at 3 D regions inside dissolve.
The surface 残 that were changed to secret code by rare codons stay the occurrence of the things, For about 15% entireness surface the 残 stay the thing to explain ( diagram2 That HAV capsid, later on is very and not too possible from it that take place A the 核甘 substitute in the rare codon lieutenant general to can give the ascension Arrive the sparse unusual happening that resemble of new codon( table4), in order arrive the maintenance That translates the dynamicses to is right of folding and have noing a loss Efficiency. In fact , at that in in times before mentioned the capsid Substitute, unique that is in the VP1 position 25( the Ile run into) From similar of-The rare changes arrives not rare and that is in the position 271 The VP1( to occupation of hundredweight) changes from to unmistakably of similar- Rare Rare. All anothers substituted to affect not rare codons.{e#oz, http://www.100md.com
An attractive dispute, however, is objection in the codon Method of using HAV is with mankind's cell, because of the tRNAs validity Host is suffer to bring up.The picornavirus model spread overs this to use The research emerges the codon method of using to resemble very much to that their host. However, this situation suggest the competition's occurrence To 於 tRNAs, at in other factor.Because PV-1 is with the FMDV- C, this competition Were avoided the quilt to proteinly synthesize the cell of in order to hide the thing's inductive method that shut Cross the carboxy cleavage of the translation's composition eIF4G Beginning 2 As are with the L proteases synthesis, respectively(22). That is still vinegar 栗核 that slice opened the eIF4G factor the right internality the protein is a live 跃 of Into make- locate most and mostly of picornaviruses translation beginning that depend on, Although that HAV need an eIF4G factor for not yet quilt person touching(6). That Comparison the latter of is a kind true of hermeneutic for in order to hide to shut its thing to 什麽 already and have no is Describe the cell that infect for HAV. Result, HAV competition To 於格 the 状 automation is a factor of uncomfortable body, at them in tRNAs; therefore, that Its the most abundant codons host is not its enrich most of with, In some instances, flatly is a rare codons.
It is particular to respond to in order to hide to shut the mechanism of its thing to lack with what that take place The number of long extracorporeal period feel to harmonize to ～ a special The codon method of using avoid the direct competition with host Cell system and concomitant admission a highly the tightly packed's capsid That make sures a high degree environment of continuously level.w9x$, 百拇医药
ÀNgels Rabass the specialty on the technique of the ó and Serveis Cient í fic- T è cnics that 巴赛隆 the 纳 's university.w9x$, 百拇医药
The partial inside of this research at investitive ERB3514PL973098 were supported, QLRT-1999-0634, with the QLRT-1999-0594 from EU; BIO99-0455 is from that CICYT, science with the technique's department, Spain; with 1997 SGR 00224 from the Generalitat dew9x$, 百拇医药
Acharya,R.,E. Fry in oil, D. Stuart, G. 福 gram 斯 , D. Rowlands is with the F. 1989. Foot-and-mouth disease of three spaces's construction Virus in 2.8:00Å Resolution. Nature337:709-716.w9x$, 百拇医药
Adzhubei, A. A., I. A. Adzhubei, I. A. Krasheninnikov is with the S. 1996. Not and as one's pleases method of using"Depravity of"Codons is Right protein of the three-dimensional space's construction speak. In February row 特 person. 399:78-82.oo, 百拇医药
Arauz- Ruiz, P., L. Sundqvist, Z. Garc í a, L. Taylor, K. Vison á, H. Norder, with the L. O. Magnius. 2001.The source that assumption is usually break outsA were had to limit at the hepatitis of the locality district that inside the preface row confirm a that VP1 district. The medicine's J.. Virol. 65:449-456.oo, 百拇医药
Bergmann, E. M., S. C. Mosimann, M. M. Chernaia, B. A. Malcolmand M. N. James. 1997. The refinement's crystal 3 Cs construction Come from the hepatitis a the virus's gene product: Specific medicine proteinase activity is with the RNA Acknowledgement. J. Virol. 71:2436-2448.oo, 百拇医药
Flourish, R., C. J. A. the fifth 音 , M. M. M. of the big 音 rank Salimans, C. L. Jansen, P. 1990. Quick with Is sour for nucleic to wash the simple method clearly. J. Clin. Microbiol. 28:495-503.
Borman, A. M. is with the K. M. Kean. 1997. Not yet quilt person eukaryotic that touchedStart the factor 4 G quilt is hepatitis a the beginning of inside virus need Translation. 滤 is over the sex microbiology237:129-136.2a-10jn, 百拇医药
Chao, L. 1990.The do exercise to keep fitting of RNA virus that quilt muller is decreasing 棘 round. Nature348:454-455.2a-10jn, 百拇医药
Rib- Mattioli, M., V. Ferre, S. Monpoeho, L. Garc í a, R. 2001. 82:2647-2652.2a-10jn, 百拇医药
Domingo, E. 1996. The biology's importance 滤 is over the sex poison 菌 of Quasispecies.滤 is over the sex poison the 菌 's rose. Pastor2:247-261.2a-10jn, 百拇医药
Emini, E. A., J. V. Hughes, D. S. Perlow is with the J. Sink in the mire 沼 . 55:836-839.2a-10jn, 百拇医药
Gavrilin, G. V., E. A. Cherkasova, G. Y. Lipskaya, O. M. Kew, V. I. Agol. 2000.Circulate the evolving of wilderness poliovirus with In an immunodeficient the vaccine in the patient get from of poliovirus: Unification a model. 74:7381-7390.2a-10jn, 百拇医药
The Hansen, J. L., A. M. hope earnestlies, with the S. C. Shultz. 1997. 5:1109-1122.
Hogle, J. M., M. Chow is with the D. J. Filman. 1985. Å Resolution. Science229:1358-1365.2.!fi^, http://www.100md.com
The Hollinger, F. B. love the 默 with S. U. to living. 2001. Hepatitis a Virus, p. 799-840. At D. M. Knipe, P. M. Howley, D. E. Griffin, R. A. Living the D of small sheep, M. A. horse, B. Roizman with the S. E. Straus( ed.), realm 滤 is over the sex microbiology, the 4 Ed., vol. 1. Lippincott William& Wilkins, Philadelphia, Pa.2.!fi^, http://www.100md.com
Ivanov, V. S., L. N. Kulik, A. E. Gabrielian, L. D. Tehikin, A. T. Kozhich, with the V. T. Ivanov. 1994. Synthesize the material 缩 the ammonia sour at that Hepatitis A T- The determination of the cell epitopes. In February row 特 person. 345:159-161.2.!fi^, http://www.100md.com
Luo, M., M. G. Rossmann, with the A. C. Palmenberg. 1988. 166:503-514.2.!fi^, http://www.100md.com
Martinez, M. A., J. Dopazo, J. Hernandez, M. G. Mateu, F. 1992. Evolving of capsid The gene of the protein feet- With the 嘴 disease virus: The antigenic variety have noes Contain the ammonia 基 sour over the accumulating of replacement decade that six 聚 . J. Virol. 66:3557-3565.
Nainan, O. V., M. A. Brinton is with the H. S. Margolis. 1992. 191:984-987.wcs{}, 百拇医药
Nei, M., with the T. Gojobori. 1986. Simple of method is Estimate the synonym of with not the synonym's 核甘 arithmetic figure Substitute. 摩尔 . Biol. Evol. 3:418-426.wcs{}, 百拇医药
Palmemberg, A. C. is with the J.- Y. Sgro. 1997. Topological Picornaviral genomes buildup: RNA covariance prediction The construction's signal. Semin. Virol. 8:231-241.wcs{}, 百拇医药
咻 ground, L.- H., with the S. M. 柠檬 . 1992. Antigenic constructionMankind's abscondence mutation that hepatitis, virus by were is heterogeneoused by choice of analysis definition The monoclonal antibody of the section of opposite 於 rat. J. Virol. 66:2208-2216.wcs{}, 百拇医药
Racaniello,V. R. 2001. Picornaviridae: That Virus is with their answer, p. 685-722. At D. M. Knipe, P. M. Howley, D. E. the Griffin, R. A. living the D of small sheep, M. A. horse, B. Roizman with the S. E. Straus(ed.), realm 滤 is over the sex microbiology, the 4 ed., vol. 1. Lippincott William&wcs{}, 百拇医药
Robertson, B. H., R. W. Jansen, B. Khanna, A. Totsuka, O. V. Nainan, G. Siegl, A. Widell, H. S. Margolis, S. Isomura, K. Ito, T. Ishiku, Y. Moritsugu, with the S. M. 柠檬 . 1992. The related hepatitis of the heredity gene a The virus weariness from overwork come froms the recovered of the different geography district. J. Virol general. 73:1365-1377.wcs{}, 百拇医药
S á nchez, G., R. M. pint ó, H. Vanaclocha is with the A. Bosch. 40:4148-4155.wcs{}, 百拇医药
Taylor, M. B. 1997. The south's numerator epidemiology Hepatitis an of nervous virus in Africa: 1982-1996. The medicine's J.. Virol. 51:273-279.wcs{}, 百拇医药
Construct, F. 1990. The valid arithmetic figure of the codons of using at Gene. Gene87:23-29.(Gl ò ria S á nchez 艾伯特 Bosch with the Rosa M. Pint ó)
Received the 2002 June 17/ the 2002 of the general acknowledgement September 24o+!q&, 百拇医药
KsIs alike to the poliovirus( PV) with the foot-and-mouth disease virus( FMDV), Ka is what size of 1 order of sequence ratio is lower. ThatNcThe parameter offering closes the information codon method of using of the 於～ the prejudice with reduce when prejudice gain. NcThe value is roughly in the HAV 38, idle away in the PV and the FMDV, it is roughly 53. 22 The emergence of the rare codons is in the front 8 moderate in the PV 7 in the FMDV disheveled hair now. Big part that keep of the strategy of rare codons P1 district the 於 that carboxy the edgeß Bucket with{alpha}o+!q&, 百拇医药
382325Inconstancy that the foundation of that numerator this inherit the gene and may be a high mistake 82325 滤 over the ratio RNA that sex poison the 菌 's RNA- suffer to bring up the polymerase correct the mechanism with nonattendance.Although have no a data to exsits on the mistake rate the HAV polymerase, variety frequency is a scope of various different RNA viruses from the each foundation replacement of each bout that 10-4 to 10-5 copy.(9)9The 9 什麽 that sour different race of nucleic of that persuasion is a sour different race does not match to contain the ammonia 基 to should rely on the lacking of nonsynonymous the variety, possiblely adequacy is to their obviation of negative choice.However, 聚 that the variety of delivering the true mold 态 , often is polluteding to unite, may lead to there to accumulating of that little tiny HAV population that food make person's crack-up.(7) 7 In the context, the low degree that that is refreshing contain the ammonia 7 基 sour in the ～ 's changes capsid the district suggest the strong construction restrict.
The current work, we began an analysis of the 核甘 And contain what ammonia 基 of sour in the ～ 's changes preface row performance that can get Strain is from the GenBank and from the insulation of a hepatitis of rare food A break out. Protein(4), the construction's model is a VP2, VP3, VP1 with 3 D The data that protein is from the reality inferences to is structural for that Poliovirus protein(13) with the foot-and-mouth disease virus (1) and from the reality of that poliovirus 3 D polymerase(12).j3y0, http://www.100md.com
Virus. Can get to GenBank of 15 complete of HAV preface the row is used in this research everywhere.These preface the row express a group of geographies of and at that time of the different HAV is tired( table1). additional,18 sharp hepatitis of strains at an a kind of consumption for break outing the inside from the patient quilt insulating the quilt coquina unite a clam.(24) 241 24 µL 浆 liquid the 抽 take the sample by the guanidine at elsewhere according to the description's thiocyanate treatment.(5,24) 524 524j3y0, http://www.100md.com
fig.ommitteed
Table 1. Complete of HAV preface row Can get at the GenBank with now use the researchue, http://www.100md.com
RT- The PCR enlarges with the 核甘 preface row. The P1-2 that that is complete the HAVs preface row insulate to is acquired at their after extend of because of thatPwo Transcribing of reverse side-( RT) PCR system( Roche) by follow behind to make the specification of the operator and because the handbook match the capsid protein genomic the district( table2). The RT of two directions- The PCR product preface row uses a Thermo Sequenase 2 2 颜料 terminator the period quilt circulate the preface row the premix by follow behind the material( the Amersham Pharmacia living the 化 technology) that manufacturing the operator's instruction with because of the ABI prism 377 in proper order 器 of automation DNA.( Perkin- elm)ue, http://www.100md.com
fig.ommitteedue, http://www.100md.com
Table 2. Handbook that used is with the circumstance because of the RT- The PCR enlarges with the HAV preface rowue, http://www.100md.com
核甘 with contain the analysis of the sour preface row of the ammonia 基 . The preface row that aim at the variety uses the ClustalW execution 19Plan by the DnaSP 19 ( 巴赛隆 the 纳 's university).
The in order to produces the codon method of using the table, poliovirus serotype for HAV 1 ( PV-1), with the foot-and-mouth disease virus serotype C,( FMDV- C) The sharp end plans( Europe of the molecular biology open the software suit) Were used.A the rare codon were defined to a the whose frequency is Little 於 30% that is in the most abundant synonym that it does ever had of the each inside that Codon method of using table(11). (Nc) measure the codon prejudice(26). ThatNc The value is always at 20( be the time that unique codon be used as availably each one to contain the ammonia 基 sour) And 61.( when the codons were aleatoricly use the timed) thatNc Plan by the 薯 ( the molecular biology of European open the software Suit).wp-&8, 百拇医药
Study to rare codon position of 於 , and the protein is inside the class's construction Electric wire details model that HAV VP2, VP3 is°which have project with VP1 From a the picornavirus aim at(16) true construction The data is nervous for PV-1 Mahoney Were increased and arrange. The three-dimensional space's model is that HAVprotomer too quilt Luo et al reasoning. (16; M. Luo, personal Communication) aim at from this. Statistics certain The position or allotment of that rare codons, a2 The frequency were take upped. The different protein is discrete Enter two districts inside: ( i) the carboxy end with the edge that is highly Construction 化 chemical element(ß Bucket with{alpha} The protein's surplus is part of. That so-called carboxy The extreme limit was is part for the third carboxied by definition that is structural Plus five close by exterior 残s stay the thing's chemical element. Instance, when thatß Bucket or that{alpha} Compare three 残s to stay the thing short, the remnant for having insidely is included; When compare five exteriors to attend there little of time the 残 stay the thing at Next the chemical element that is structural, total that attend the district Were included.If the short cut is worth a, contain rare codons conservancy At exceed 50% of the preface row inside is included in the ～ this research. At that2 Rare codons. PV-1 is with the FMDV- C true construction Capsid protein And), Recombinant HAV 3 C proteases true construction,() And HAV 3 D polymerases a models inference from the recombinant PV3D protein Used to the position's comparison analysis of that is rare Codons.
The value that logarithms( P- Num) have relation with ～ is different HM-175 genomic too the district that HAV is The nervous PV-1 were acquired from.4i, 百拇医药
核甘 preface the row arrive the number.P1-2 a 核甘 the18 preface row the insulation unite from that clam of Break out to is in the GenBank to deposit and have the quilt the allotment to arrive Arithmetic figureAF396391 AF396408.4i, 百拇医药
HAV of generally describe to insulate the hepatitis that unite from that clam on break outing. All 18 insulate to belong to the genotype IB, although 6 in the outside that 18 samples had to keep of contain the sour variety( Val arrive Ile) of the ammonia 基 in the remnant 72, in the VP3 preface the row's central inside, positive and participant in the immunodominant position.(24) 24This variety lures on losing the monoclonal antibody the antigenic K34C8 acknowledgement and like this expressing the occurrence to change. Two sour varieties that containing the ammonia 24 基 of affixtureses are disheveled hair now, in the VP2 position 40( to Ala Val at two strain) with the VP1 position 28.( run into the Val at the inside strain that a 核甘 ) that all are same alike to arrange in this 18 samples from 97.85 to 100% in the P1-2 an inside district, be to contain what ammonia the 基 's sour time same alike arrange from 99.75% to 100%s.
In the capsid frequency in the district is with the type variety. ThatKs AndKaIt is worth a to is°which have project to combination those second HAVs In the capsid preface in the district row( table3). Ks Value is Break out the preface row to is 7.5 times at the VP0 to with VP3 lower Low capsid district with 5 times are in the VP1-2 a district comparison that KsThe value is that GenBank preface row, when thatKa Value is 13.4,3, and 16 times lower, respectively.These consequently instructionses GenBank preface the row's cluster of high rift comparison Break out the preface row. ThatKs/Ka The ratio break outs the preface row for these Feel to kill is high to VP0 with the VP1-2 a district is with the immensely For the VP3 district high degree. The lower ratio of ratio observes for VP3 The district reflects what that relatively enrich(18 inside of 6 preface row) The antigenic change's occurrence in the top to describe. For that GenBank preface row, ratio right all is too very high That analyzed the genomic district. When complete of capsid district ( P1 district) HAV is with the FMDV-The C is compared, and generally discovers When thatKs The value is alike in two viruses, thatKa In the FMDV- C. The inside consequently is 1 order of sequence of high size is, that Ks/KaThe ratio is important high in the HAV( table3). While resembling of After conclusion is distressed in the value's a comparison for that HAV VP1 district, FMDV- C, with the PV-1( table3).
fig.ommitteed'ez, 百拇医药
Table 3. The variety's analysis at HAV preface row'ez, 百拇医药
Codon method of using. Later on is the most widespread from the synonym's variety to moderate the such variety occurrence to suffer the system 於 that influence codon the method of using in the HAV, in the method of using in the HAV an analysis take up.Complete of the beguilement genome study the preface row for GenBank quilt.10 5 included the synonym to emerge the usage of the rare codonsed from codons 18 sour family for containing the ammonia 基 ( table4). 4). 10 8 from these 20 rare codonses are row of similar to ～ that GenBank prefaceses of those, with 4 more( Arg:'ez, 百拇医药
fig.ommitteed'ez, 百拇医药
Table 4. Codons percentage because of Concern towards at HAV with mankind's cell codon inside the most abundant synonym Method of using table'ez, 百拇医药
NcWorth a, is 39 於s total amounts to cheat the district,38.8 for the capsid district, with 38.7 for the nonstructural district. ThatNcEvaluate the district for capsid at that break out the preface row is 38.9.These worth a designation that have no a codon method of using important and different prejudice at that in closely related break out the preface row with the GenBank preface row. ThatNcThe value also is computed for two others picornaviruses, PV-1 with FMDV- C( table5). Because of these two viruses, markedly compare higherNcThe worth a quilt acquires(52.6 with 52.1, respectively, for the HAV VP1 and 5 ～相 than 37.2;53.3 with 38.8 於s the P1FMDV of whole- C is with the HAV district, respectively), the designation HAV have a codon method of using high and a lot of prejudices. The further quilt of this fact confirms to be contained the ammonia 基 sour family of the arithmetic figure include rare codons or were compared by that clearly rare codons of high total amount is in the HAV compare in the another virus( table5). 5
fig.ommitteed1#, 百拇医药
Table 5. Codon method of using is three picornaviruses1#, 百拇医药
4). for those three surplus of two times grounds deteriorate to contain the ammonia 基 sour, and the Lys, Gln may bind with Glu, each codon two tRNAs with unique anticodon quilt sharing; have no clarity of codon is partial to is shown by the HAV.For the codon triple deteriorate the Ile, the most abundant mankind to may bind two tRNAses, whose anticodons quilt sharing by two alternative plan codons; the second the most abundant codon may bind three anticodons( two sharing with an unshared); may bind with most without the abundant codon two anticodons.( penny enjoy and unshared)In this kind of situation, the codon HAV choice is such as the big part abundant to have an unshared codon anticodon and that are not rare to host cells. Same alike of the strategy were observed because of big part those four- And six times's depravities contain the ammonia 基 sour, although in some insides, for example the Val choose the rare and human codon with second monetary unit, HAV of Rome 尼 to consider as its enrich most of, have one's own the unshared other possible of codons hereafter the anticodon match most human codons that enrich, such competition of mightiness performance.
The position of the rare codons. The position of the rare codons is in the GenBank preface the row is inside is Study, although it is only the amount that codons consider the rare that Is current with rare at both all the GenBank moderate the hepatitis Break out the preface row( table4). Exceed 50% of analysis preface the row pass for the importance Reign to place the inside, and study.All,60 rare codonses be amounted by 764 The codons were kept in the P1 districts, and express 7.8% keep Rare codons.When urgently increase in the aegis To 85 or 100%,2.7 or 0.9%, respectively, total amount The P1 codons is a rare codons. It should notice that 7 in the outside This 60 rare codons(11.6%) quilts keep the group in whole Preface row.In some instances, the each one person that preface row is lacking Rare codon contain rare codon concluding the other that tie the possibility to near to ( a to three codonses distance), increase by the percentage aegis. Therefore,26 highly kepted the position should be very Turning point of were recognized out in the construction's genome.
The incline toing of ～ were located that in the carboxy extreme limit highly Constitute the chemical element(ß Bucket with{alpha} ( diagram1). All,52.7% of capsid district rare codons 於 carboxy extreme limit thatß Bucket And{alpha} 37.6% total polyprotein. The incline toing of ～ were located There importance for carboxy extreme limit statisticsing(P < 0.05). FMDV- C district with for the PV-1 VP1 district. An importance of Nonrandom position must not at too FMDV- The C inside is disheveled hair now or PV-1, although at both inside the virus is partial to to carboxy The extreme limit also is observed.:&ask1, 百拇医药
fig.ommitteed:&ask1, 百拇医药
Figure 1. The construction's VP2, VP3 is with the VP1 Electric wire details the model is a PV-1 from the data reasoning that true. (Mahoney):&ask1, 百拇医药
1). ßThe D quickly go forwardses, with the third along short attended to prolong the of row at that of all prefacesßF and thatßThe G1 quickly go forwardses.In the VP3 district, a the gathering is disheveled hair to only start now at that beforeßG2 bucket end for with in the construction's 後 only. In the VP1 district, a group of containing of 於 protein the terminal point of the ammonia 基 , with two time for drive locating at ～ ending thatßE bucket with at attend the preface row the of person at thatßE bucket with that{alpha} The B is spiral.Break out the preface row to not is included to arrive to avoid to be make sured by the latent prejudice of their be over of 於 relate to; however, their habit the position of the esse turning point in this analysis( diagram1). 1
Allly were changed to containing of secret code the ammonia 基 by these sour to all is located In the revelation capsid district( diagram2), and these come together Include very rare codons. Frequency these are very rare The codons is that their the most usual codon under 20% Family or even under 5% in some instances, for example that ThatßG2VP3 cluster.It should be recorded that not The codons for having first cluster besides outside some ones are rare also change to secret code The 残 of locating stays the thing at that on surface. All,67% of all are rare The codons changed to secret code the 残 to stay the thing in the capsid to superficially expose, more Accurate of,81,72, and 64% of VP2, VP3 is with the rare codons of VP1, Respectively. On the other hand,60% these rare codons is Highly keep at at least 85% GenBank preface row.$, 百拇医药
fig.ommitteed$, 百拇医药
Figure 2. Capsid surface position Were changed to containing of secret code the ammonia 基 by rare codons keeping sour in the HAV protomer Refinement model. ( Luo, individual communication) grillage, pink, with 蓝色 that the orb that 残 instructions VP2, VP3 stay the thing with the VP1, Respectively, the rare codons of quilt change to secret code. The yellow orb matches Arrive the 残 to stay the thing in the antigenic position to produce the relation.
The RNA composing of the inside class. Although the development's kind that RNA the genome avoid an exactitude of The prediction, P of the construction of its inside class-The Num is worth a to provide The tendency's quantity judges a then arrive the double make the foundation Together break the layer in suboptimal a collections with the partner of possibility other (20). RNA district with ～ contain abundant foundation low P- Num value (P-Num,<100) Were predicted the second construction of containment (20). This parameter has to plan any for the total genome HM-175, HAV strain or for the part's RNA district. Although There is P-The Num foundation percentage is worth a<100 Is 24.15%, The style quilt of a clarity observes at in different genomic District( table6). There is low P- The Num foundation value were observed in the P3 districts More moderate even to compare in the noncoding district in the P1 district, Tight construction of proposal is in that P3 district. Ratio In the different district P-Of the Num value is°which have project Because HAV is with the PV-1.P3 district/ P1 the district compare is 2.3 with 1.7, respectively, P3 district/5' noncoding district ratio Is 1.6 with 1.7, respectively, with the P1 district/5' noncoding The district compares is 0.7 with 1, respectively.These compare to suggest RNA that HAV P1 the district reach on comparatively comparing lower P- Num value with right should of a relatively looser composing.
fig.ommitteed6)4|, 百拇医药
Table 6. Validity ofNc6)4|, 百拇医药
14However, the antigenic change to have to is for them to choose to different MAbs of resisting of ～ .(18,21)1821At that in unite from the clam of break out to insulate, a the natural antigenic change to have disheveled hair now which lure the MAb K34C8 with the on-line epitope VP1 of a loss of the acknowledgement of a kind of the second variety.(24) 24However, the nonsynonymous frequency change to observe to compare those in the HAV importance of low picornaviruses is discovereds in others, for example PV-1 with FMDV. All, on place( remnant 5) in the VP4ing, four positions are in the VP2, in the VP3 of nine position( the 1821 24 残 stay the thing 25,28,148,156,174,208,216,241, with 271) that six position( the 残 stay the thing 32,45,72,92,145, with 239), with perform the inconstancy at the GenBank with break out the preface row the inside in the VP1. 1015 With the position 72 VP3.(18,21,24) 182124Additional, preface row that VP1 position 174 were located at come from the 1015 182124 残 to stay the thing 171 central to 176 the immunodominant position of this proteins, HAV of partially is which, although have no a data to epitope in containing of this position 意 on esse construction.(18,21) 1821Same alike of the situation apply the 1821 於残 to stay the thing 148,156, VP3 of and VP1 is with the remnant 145 inside of 241, is located in the partial 残 that the ～ that neighborhood is a HAV immunodominant position stay the thing in the HAV model of construction inside(16; Luo,16The individual's communication). in addition, the 16 残 stay the thing 208 with the VP1 inside of 216 in the ～ of nearby is located the remnant 221, define HAV a the second antigenic the position.(18,21) 182124 Then the extensive replacement that it can be expected that more right emergence is essential a the new serotype is with the replacement that that such to were is is sturdylied by bar structural restrict. 1821 24
The idea of general restrict of the strong capsid construction possibility Is a lot of usages of the rare codonses of quilts with protect to enhance, The whose strategy position contain quilt to request to produce the codon Context variety along mRNA, respond the ～ 's decrease translation Accelerate with the admission appropriate of protein fold of. ThatNc The value acquires Instructions to different picornaviruses of 於 a the importance's comparison highland Prejudice is in the codon method of using the aspect compare in the PV-1 or FMDV in the HAV- C. Gene inside because of The ratio is lowerNc The synonym's codons compares the highland to use the ～ and ～相 than geneNc Value, Have in the comparison in the usage that synonym that codons is very stick of 柔 (26). It may were supposed that low pointNc The value suggests usages to like better Codons and, result, the esse of the rare codons. Does the codon method of using designation is a synonym and may side with direction The part links the realm to is inside with the rare codons of the old customer the classes of Construction area segment(2,11). The rare codons of nonrandom allotment can be observed at that Capsid district, were ended by true carboxy of position like bettering And edge that highly constitute the protein chemical element. In the difference, Incline to not have the quilt to observe at 3 C region or flat At 3 in the D region, full of at 100% kept the rare codons Compare the P1 district. However, by the usage P- Num value that HM-175 strains is observed for the HAV, it such as the reference that for 3 constructions that D regions, RNA is inside classes are tight; result, Row of its preface should to ～ is not more couchant inconstancy, consider as is For the other virus proposal(11). 3 10 percentage with 64% of P1 district with 3 rare codons of D regions, respectively, is Use the low P- The Num value immerses in the RNA districts.( the data does not show) The result, it may be these rare codons games that considereds A dual role is all with protein in the maintenance RNA aspect construction, In the protein in the P1 level more important district with At the RNA at 3 D regions inside dissolve.
The surface 残 that were changed to secret code by rare codons stay the occurrence of the things, For about 15% entireness surface the 残 stay the thing to explain ( diagram2 That HAV capsid, later on is very and not too possible from it that take place A the 核甘 substitute in the rare codon lieutenant general to can give the ascension Arrive the sparse unusual happening that resemble of new codon( table4), in order arrive the maintenance That translates the dynamicses to is right of folding and have noing a loss Efficiency. In fact , at that in in times before mentioned the capsid Substitute, unique that is in the VP1 position 25( the Ile run into) From similar of-The rare changes arrives not rare and that is in the position 271 The VP1( to occupation of hundredweight) changes from to unmistakably of similar- Rare Rare. All anothers substituted to affect not rare codons.{e#oz, http://www.100md.com
An attractive dispute, however, is objection in the codon Method of using HAV is with mankind's cell, because of the tRNAs validity Host is suffer to bring up.The picornavirus model spread overs this to use The research emerges the codon method of using to resemble very much to that their host. However, this situation suggest the competition's occurrence To 於 tRNAs, at in other factor.Because PV-1 is with the FMDV- C, this competition Were avoided the quilt to proteinly synthesize the cell of in order to hide the thing's inductive method that shut Cross the carboxy cleavage of the translation's composition eIF4G Beginning 2 As are with the L proteases synthesis, respectively(22). That is still vinegar 栗核 that slice opened the eIF4G factor the right internality the protein is a live 跃 of Into make- locate most and mostly of picornaviruses translation beginning that depend on, Although that HAV need an eIF4G factor for not yet quilt person touching(6). That Comparison the latter of is a kind true of hermeneutic for in order to hide to shut its thing to 什麽 already and have no is Describe the cell that infect for HAV. Result, HAV competition To 於格 the 状 automation is a factor of uncomfortable body, at them in tRNAs; therefore, that Its the most abundant codons host is not its enrich most of with, In some instances, flatly is a rare codons.
It is particular to respond to in order to hide to shut the mechanism of its thing to lack with what that take place The number of long extracorporeal period feel to harmonize to ～ a special The codon method of using avoid the direct competition with host Cell system and concomitant admission a highly the tightly packed's capsid That make sures a high degree environment of continuously level.w9x$, 百拇医药
ÀNgels Rabass the specialty on the technique of the ó and Serveis Cient í fic- T è cnics that 巴赛隆 the 纳 's university.w9x$, 百拇医药
The partial inside of this research at investitive ERB3514PL973098 were supported, QLRT-1999-0634, with the QLRT-1999-0594 from EU; BIO99-0455 is from that CICYT, science with the technique's department, Spain; with 1997 SGR 00224 from the Generalitat dew9x$, 百拇医药
Acharya,R.,E. Fry in oil, D. Stuart, G. 福 gram 斯 , D. Rowlands is with the F. 1989. Foot-and-mouth disease of three spaces's construction Virus in 2.8:00Å Resolution. Nature337:709-716.w9x$, 百拇医药
Adzhubei, A. A., I. A. Adzhubei, I. A. Krasheninnikov is with the S. 1996. Not and as one's pleases method of using"Depravity of"Codons is Right protein of the three-dimensional space's construction speak. In February row 特 person. 399:78-82.oo, 百拇医药
Arauz- Ruiz, P., L. Sundqvist, Z. Garc í a, L. Taylor, K. Vison á, H. Norder, with the L. O. Magnius. 2001.The source that assumption is usually break outsA were had to limit at the hepatitis of the locality district that inside the preface row confirm a that VP1 district. The medicine's J.. Virol. 65:449-456.oo, 百拇医药
Bergmann, E. M., S. C. Mosimann, M. M. Chernaia, B. A. Malcolmand M. N. James. 1997. The refinement's crystal 3 Cs construction Come from the hepatitis a the virus's gene product: Specific medicine proteinase activity is with the RNA Acknowledgement. J. Virol. 71:2436-2448.oo, 百拇医药
Flourish, R., C. J. A. the fifth 音 , M. M. M. of the big 音 rank Salimans, C. L. Jansen, P. 1990. Quick with Is sour for nucleic to wash the simple method clearly. J. Clin. Microbiol. 28:495-503.
Borman, A. M. is with the K. M. Kean. 1997. Not yet quilt person eukaryotic that touchedStart the factor 4 G quilt is hepatitis a the beginning of inside virus need Translation. 滤 is over the sex microbiology237:129-136.2a-10jn, 百拇医药
Chao, L. 1990.The do exercise to keep fitting of RNA virus that quilt muller is decreasing 棘 round. Nature348:454-455.2a-10jn, 百拇医药
Rib- Mattioli, M., V. Ferre, S. Monpoeho, L. Garc í a, R. 2001. 82:2647-2652.2a-10jn, 百拇医药
Domingo, E. 1996. The biology's importance 滤 is over the sex poison 菌 of Quasispecies.滤 is over the sex poison the 菌 's rose. Pastor2:247-261.2a-10jn, 百拇医药
Emini, E. A., J. V. Hughes, D. S. Perlow is with the J. Sink in the mire 沼 . 55:836-839.2a-10jn, 百拇医药
Gavrilin, G. V., E. A. Cherkasova, G. Y. Lipskaya, O. M. Kew, V. I. Agol. 2000.Circulate the evolving of wilderness poliovirus with In an immunodeficient the vaccine in the patient get from of poliovirus: Unification a model. 74:7381-7390.2a-10jn, 百拇医药
The Hansen, J. L., A. M. hope earnestlies, with the S. C. Shultz. 1997. 5:1109-1122.
Hogle, J. M., M. Chow is with the D. J. Filman. 1985. Å Resolution. Science229:1358-1365.2.!fi^, http://www.100md.com
The Hollinger, F. B. love the 默 with S. U. to living. 2001. Hepatitis a Virus, p. 799-840. At D. M. Knipe, P. M. Howley, D. E. Griffin, R. A. Living the D of small sheep, M. A. horse, B. Roizman with the S. E. Straus( ed.), realm 滤 is over the sex microbiology, the 4 Ed., vol. 1. Lippincott William& Wilkins, Philadelphia, Pa.2.!fi^, http://www.100md.com
Ivanov, V. S., L. N. Kulik, A. E. Gabrielian, L. D. Tehikin, A. T. Kozhich, with the V. T. Ivanov. 1994. Synthesize the material 缩 the ammonia sour at that Hepatitis A T- The determination of the cell epitopes. In February row 特 person. 345:159-161.2.!fi^, http://www.100md.com
Luo, M., M. G. Rossmann, with the A. C. Palmenberg. 1988. 166:503-514.2.!fi^, http://www.100md.com
Martinez, M. A., J. Dopazo, J. Hernandez, M. G. Mateu, F. 1992. Evolving of capsid The gene of the protein feet- With the 嘴 disease virus: The antigenic variety have noes Contain the ammonia 基 sour over the accumulating of replacement decade that six 聚 . J. Virol. 66:3557-3565.
Nainan, O. V., M. A. Brinton is with the H. S. Margolis. 1992. 191:984-987.wcs{}, 百拇医药
Nei, M., with the T. Gojobori. 1986. Simple of method is Estimate the synonym of with not the synonym's 核甘 arithmetic figure Substitute. 摩尔 . Biol. Evol. 3:418-426.wcs{}, 百拇医药
Palmemberg, A. C. is with the J.- Y. Sgro. 1997. Topological Picornaviral genomes buildup: RNA covariance prediction The construction's signal. Semin. Virol. 8:231-241.wcs{}, 百拇医药
咻 ground, L.- H., with the S. M. 柠檬 . 1992. Antigenic constructionMankind's abscondence mutation that hepatitis, virus by were is heterogeneoused by choice of analysis definition The monoclonal antibody of the section of opposite 於 rat. J. Virol. 66:2208-2216.wcs{}, 百拇医药
Racaniello,V. R. 2001. Picornaviridae: That Virus is with their answer, p. 685-722. At D. M. Knipe, P. M. Howley, D. E. the Griffin, R. A. living the D of small sheep, M. A. horse, B. Roizman with the S. E. Straus(ed.), realm 滤 is over the sex microbiology, the 4 ed., vol. 1. Lippincott William&wcs{}, 百拇医药
Robertson, B. H., R. W. Jansen, B. Khanna, A. Totsuka, O. V. Nainan, G. Siegl, A. Widell, H. S. Margolis, S. Isomura, K. Ito, T. Ishiku, Y. Moritsugu, with the S. M. 柠檬 . 1992. The related hepatitis of the heredity gene a The virus weariness from overwork come froms the recovered of the different geography district. J. Virol general. 73:1365-1377.wcs{}, 百拇医药
S á nchez, G., R. M. pint ó, H. Vanaclocha is with the A. Bosch. 40:4148-4155.wcs{}, 百拇医药
Taylor, M. B. 1997. The south's numerator epidemiology Hepatitis an of nervous virus in Africa: 1982-1996. The medicine's J.. Virol. 51:273-279.wcs{}, 百拇医药
Construct, F. 1990. The valid arithmetic figure of the codons of using at Gene. Gene87:23-29.(Gl ò ria S á nchez 艾伯特 Bosch with the Rosa M. Pint ó)