Equine Herpesvirus 1 Utilizes a Novel Herpesvirus
http://www.100md.com
病菌学杂志 2005年第5期
Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana
ABSTRACT
The well-described herpesvirus entry receptors HveA (TNFRSF14), HveB (nectin 2), and HveC (nectin 1) have been shown to mediate the entry of alphaherpesviruses. Our findings showed that the alphaherpesvirus equine herpesvirus 1 (EHV-1) efficiently entered and replicated in CHO-K1 cells that lack the entry receptors HveA, HveB, and HveC, demonstrating that EHV-1 utilizes a unique entry receptor. As with other alphaherpesviruses, efficient EHV-1 entry was dependent on glycoprotein D and cell surface glycosaminoglycans.
TEXT
Equine herpesvirus 1 (EHV-1), a member of the Alphaherpesvirus subfamily, is the causative agent of respiratory distress, abortion, and neurological disease in horses (1). Although many aspects of the virus life cycle have been very well characterized (15), the early events in virus attachment and entry have not been systematically investigated. In particular, while entry receptors for several other alphaherpesviruses, including herpes simplex virus type 1 and 2 (HSV-1 and HSV-2), pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1) have been identified, the ability of EHV-1 to use the same or different entry receptors is unknown.
HveA is a member of the tumor necrosis factor (TNF) receptor family and mediates entry of HSV-1 and HSV-2, but not PRV or BHV-1 (11). HveC (nectin 1) belongs to the immunoglobulin superfamily and mediates entry of all of these alphaherpesviruses (6). HveB, another immunoglobulin superfamily member, is also a receptor for PRV, HSV-2, and the Rid1 variant of HSV-1 (22). In addition to HveA, HveB, and HveC, a modified form of heparan sulfate, 3-O-sulfated heparan sulfate, can mediate the entry of HSV-1 (17). All of the receptors are recognized by glycoprotein D (gD) that in turn initiates the entry process (3, 7-9, 23).
While a specific entry receptor has yet to be characterized for EHV-1, studies have shown that EHV-1 uses the same subset of viral glycoproteins utilized by other alphaherpesviruses for binding and entry into permissive cells. Similar to HSV-1, positively charged residues in EHV-1 gB and gC bind to heparan sulfate (HS) moieties on the cell surface (16, 19). After initial attachment, EHV-1 gD is required for virus entry, but no description of its putative cognate receptor has been reported. In addition to gD, gB is also essential for virus penetration, growth, and cell-to-cell spread (13). gH and gL are essential for HSV-1 and HSV-2 entry (12, 18, 20), but whether these glycoproteins play a similar role in the EHV-1 entry pathway is unknown.
The aim of this study was to ascertain whether EHV-1 utilizes the same or novel entry receptor(s) compared with other well-characterized alphaherpesviruses. To this end, the infectivity of EHV-1 on a panel of cell lines that express different virus receptors was compared to the known infectivity patterns of other alphaherpesviruses. These cell lines included HSV-1- permissive cells CHO-A (HveA), CHO-C (HveC), and Vero, EHV-1-permissive rabbit kidney cell line RK13, and HSV-1-resistant cell lines CHO-K1 and J1.1-2.
CHO-K1, CHO-A, CHO-C, RK13, and Vero cells were infected with a recombinant EHV-1 (L11gIgE), derived from the RacL11 strain, that expresses lacZ (5), and the cells were stained with 5-bromo-4-chloro-3-indolyl-?-D-galactopyranoside (X-Gal) 7 h postinfection (p.i.) to assess entry. L11gIgE efficiently entered RK13, CHO-K1, CHO-A, and CHO-C cells but exhibited severely impaired entry into Vero cells (Fig. 1A). In contrast, an HSV-1 recombinant that expresses lacZ (QOZHG) (2) did not infect CHO-K1 cells but efficiently entered all other cell lines that express at least one of the HSV-1 entry receptors (Fig. 1B). At the same multiplicity of infection (MOI), L11gIgE was further shown to enter another HSV-resistant cell line, J1.1-2 (Fig. 1C), as well as HSV-1-resistant CHO-B (HveB) cells (data not shown). An EHV-1 recombinant derived from the KyA strain, KyAgp2 (21), also efficiently entered CHO-K1 and J1.1-2 cells (data not shown). These data showed that EHV-1 entry into cells is independent of any of the known alphaherpesvirus receptors. In addition, the ability of two EHV-1 strains to efficiently enter two different HSV-resistant cell lines, CHO-K1 and J1.1-2, suggests a common mechanism for EHV-1 entry into these cells which is not strain specific. However, from these data, it is unclear whether EHV-1 is utilizing one common entry receptor or two different receptors on these cells.
Previous studies by Csellner et al. showed that EHV-1 gD is essential for EHV-1 entry into permissive RK13 cells (4). To examine whether EHV-1 gD is required for entry into HSV receptor-negative cells, CHO-K1 cells were infected with a gD-null virus EHV-1gD (derived from the HVS25A strain) (4). Complemented EHV-1gD was passed through noncomplementing RK13 or EHV-1 gD-expressing RK13 (RKgD) cells, and clarified infected-cell lysates were used to infect CHO-K1, Vero, or RK13 cells. As shown in Fig. 2, gD-complemented virus from RKgD cells [EHV-1gD(gD+)] was able to efficiently enter CHO-K1 and RK13 cells, while only a few lacZ+ cells were observed on infection with noncomplemented virus [EHV-1gD(gD–)]. These data supported the conclusion that gD is required for efficient entry of EHV-1 into HSV receptor-negative cells.
In addition to gD, efficient EHV-1 entry also required the expression of glycosaminoglycans (GAGs), since CHO-K1 cells deficient in GAG synthesis (pgsA745) (10) were poorly infected with EHV-1 after a 2-h attachment phase (Fig. 3). However, the presence of cell surface GAGs was not sufficient for entry, since GAG-expressing Vero cells were highly resistant to EHV-1 infection. Entry of EHV-1 into CHO-K1 cells occurred rapidly, and the kinetics of EHV-1 entry into CHO-K1 cells were similar to that of EHV-1 on the standard permissive host cell line, RK13 (Fig. 3). These data corroborate previous work showing that GAG receptor binding is essential for efficient alphaherpesvirus entry (16, 18, 19).
To assay the ability of EHV-1 to replicate in CHO cells, a one-step growth assay was performed. CHO-K1, CHO-A, CHO-C, Vero, or RK13 cells were infected with L11gIgE at an MOI of 1 (Fig. 4). Cells were washed with acidic buffer at 2 h p.i., and the titers of supernatants harvested at various time points were determined in RK13 cells. At 8 h p.i., the virus titers were similar for CHO-K1, CHO-A, and CHO-C cells, while the titers in Vero cells were reduced 533-fold compared to those in CHO-K1 cells. The reduced titers in Vero cells at early time points corresponded with the decreased entry kinetics of EHV-1 in Vero cells (Fig. 3); however, there was no postentry block to replication after EHV-1 entry in these cells. EHV-1 titers in RK13 cells reached a maximum of 3.27 x 107 PFU/ml at 48 h p.i. Compared to EHV-1 titers in RK13 cells, EHV-1 titers in CHO-K1 cells were reduced 72-fold, reaching a maximum of 4.53 x 105 PFU/ml at 48 h p.i. The maximum titers in Vero cells were reduced 744-fold compared to titers in RK13 cells and were reduced 10-fold compared to titers in CHO-K1 cells. These data show that EHV-1 can productively replicate and produce progeny virus in CHO-K1 cells.
Interestingly, PRV and HSV-2 were previously shown to enter CHO-K1 cells (14, 24). However, entry into these cells was greatly enhanced when one of the alphaherpesvirus receptors was expressed (6, 14). Future studies will examine whether the entry receptor utilized by EHV-1 on CHO-K1 cells is similar or distinct from the receptor(s) recognized by HSV-2 and PRV.
In summary, EHV-1 entry is mediated by an uncharacterized receptor that is distinct from all of the previously identified alphaherpesvirus receptors. EHV-1 entry into HSV-resistant cells is dependent upon gD expression, and entry is greatly enhanced in cells that express GAGs. Current experiments are aimed at identifying the EHV-1 entry receptor or receptors.
ACKNOWLEDGMENTS
We thank Millar Whalley for generously providing the EHV-1gD virus and the complementing RKgD cell line. We thank Patricia Spear for generously providing the CHO-A, CHO-B, and CHO-C cell lines. We thank Gabriella Campadelli-Fiume for kindly providing the J1.1-2 cells.
This work was supported in part by a Program of Excellence in Gene Therapy grant (HL66949-01) from NIH/NHLBI, an R01 grant (NS044323) from NIH, and grants AI22001 and P20-RR018724 from NIH.
REFERENCES
Allen, G. P., and J. T. Bryans. 1986. Molecular epizootiology, pathogenesis, and prophylaxis of equine herpesvirus-1 infections. Prog. Vet. Microbiol. Immunol. 2:78-144.
Chen, X., J. Li, M. Mata, J. Goss, D. Wolfe, J. C. Glorioso, and D. J. Fink. 2000. Herpes simplex virus type 1 ICP0 protein does not accumulate in the nucleus of primary neurons in culture. J. Virol. 74:10132-10141.
Cocchi, F., M. Lopez, L. Menotti, M. Aoubala, P. Dubreuil, and G. Campadelli-Fiume. 1998. The V domain of herpesvirus Ig-like receptor (HIgR) contains a major functional region in herpes simplex virus-1 entry into cells and interacts physically with the viral glycoprotein D. Proc. Natl. Acad. Sci. USA 95:15700-15705.
Csellner, H., C. Walker, J. E. Wellington, L. E. McLure, D. N. Love, and J. M. Whalley. 2000. EHV-1 glycoprotein D (EHV-1 gD) is required for virus entry and cell-cell fusion, and an EHV-1 gD deletion mutant induces a protective immune response in mice. Arch. Virol. 145:2371-2385.
Frampton, A. R., Jr., P. M. Smith, Y. Zhang, T. Matsumura, N. Osterrieder, and D. J. O'Callaghan. 2002. Contribution of gene products encoded within the unique short segment of equine herpesvirus 1 to virulence in a murine model. Virus Res. 90:287-301.
Geraghty, R. J., C. Krummenacher, G. H. Cohen, R. J. Eisenberg, and P. G. Spear. 1998. Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 280:1618-1620.
Johnson, D. C., and M. W. Ligas. 1988. Herpes simplex viruses lacking glycoprotein D are unable to inhibit virus penetration: quantitative evidence for virus-specific cell surface receptors. J. Virol. 62:4605-4612.
Johnson, R. M., and P. G. Spear. 1989. Herpes simplex virus glycoprotein D mediates interference with herpes simplex virus infection. J. Virol. 63:819-827.
Krummenacher, C., A. V. Nicola, J. C. Whitbeck, H. Lou, W. Hou, J. D. Lambris, R. J. Geraghty, P. G. Spear, G. H. Cohen, and R. J. Eisenberg. 1998. Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry. J. Virol. 72:7064-7074.
Lidholt, K., J. L. Weinke, C. S. Kiser, F. N. Lugemwa, K. J. Bame, S. Cheifetz, J. Massague, U. Lindahl, and J. D. Esko. 1992. A single mutation affects both N-acetylglucosaminyltransferase and glucuronosyltransferase activities in a Chinese hamster ovary cell mutant defective in heparan sulfate biosynthesis. Proc. Natl. Acad. Sci. USA 89:2267-2271.
Montgomery, R. I., M. S. Warner, B. J. Lum, and P. G. Spear. 1996. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell 87:427-436.
Muggeridge, M. I. 2000. Characterization of cell-cell fusion mediated by herpes simplex virus 2 glycoproteins gB, gD, gH and gL in transfected cells. J. Gen. Virol. 81:2017-2027.
Neubauer, A., B. Braun, C. Brandmuller, O. R. Kaaden, and N. Osterrieder. 1997. Analysis of the contributions of the equine herpesvirus 1 glycoprotein gB homolog to virus entry and direct cell-to-cell spread. Virology 227:281-294.
Nixdorf, R., J. Schmidt, A. Karger, and T. C. Mettenleiter. 1999. Infection of Chinese hamster ovary cells by pseudorabies virus. J. Virol. 73:8019-8026.
O'Callaghan, D. J., and N. Osterrieder. 1999. The equine herpesviruses, p. 508-515. In R.G. Webster and A. Granoff (ed.), Encyclopedia of virology. Harcourt Brace, San Diego, Calif.
Osterrieder, N. 1999. Construction and characterization of an equine herpesvirus 1 glycoprotein C negative mutant. Virus Res. 59:165-177.
Shukla, D., J. Liu, P. Blaiklock, N. W. Shworak, X. Bai, J. D. Esko, G. H. Cohen, R. J. Eisenberg, R. D. Rosenberg, and P. G. Spear. 1999. A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 99:13-22.
Spear, P. G. 1993. Entry of alphaherpesviruses into cells. Semin. Virol. 4:167-180.
Sugahara, Y., T. Matsumura, Y. Kono, E. Honda, H. Kida, and K. Okazaki. 1997. Adaptation of equine herpesvirus 1 to unnatural host led to mutation of the gC resulting in increased susceptibility of the virus to heparin. Arch. Virol. 142:1849-1856.
Turner, A., B. Bruun, T. Minson, and H. Browne. 1998. Glycoproteins gB, gD, and gHgL of herpes simplex virus type 1 are necessary and sufficient to mediate membrane fusion in a Cos cell transfection system. J. Virol. 72:873-875.
von Einem, J., J. Wellington, J. M. Whalley, K. Osterrieder, D. J. O'Callaghan, and N. Osterrieder. 2004. The truncated form of glycoprotein gp2 of equine herpesvirus 1 (EHV-1) vaccine strain KyA is not functionally equivalent to full-length gp2 encoded by EHV-1 wild-type strain RacL11. J. Virol. 78:3003-3013.
Warner, M. S., R. J. Geraghty, W. M. Martinez, R. I. Montgomery, J. C. Whitbeck, R. Xu, R. J. Eisenberg, G. H. Cohen, and P. G. Spear. 1998. A cell surface protein with herpesvirus entry activity (HveB) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus. Virology 246:179-189.
Whitbeck, J. C., C. Peng, H. Lou, R. Xu, S. H. Willis, M. Ponce de Leon, T. Peng, A. V. Nicola, R. I. Montgomery, M. S. Warner, A. M. Soulika, L. A. Spruce, W. T. Moore, J. D. Lambris, P. G. Spear, G. H. Cohen, and R. J. Eisenberg. 1997. Glycoprotein D of herpes simplex virus (HSV) binds directly to HVEM, a member of the tumor necrosis factor receptor superfamily and a mediator of HSV entry. J. Virol. 71:6083-6093.
Zago, A., and P. G. Spear. 2003. Differences in the N termini of herpes simplex virus type 1 and 2 gDs that influence functional interactions with the human entry receptor nectin-2 and an entry receptor expressed in Chinese hamster ovary cells. J. Virol. 77:9695-9699.(Arthur R. Frampton Jr., W)
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana
ABSTRACT
The well-described herpesvirus entry receptors HveA (TNFRSF14), HveB (nectin 2), and HveC (nectin 1) have been shown to mediate the entry of alphaherpesviruses. Our findings showed that the alphaherpesvirus equine herpesvirus 1 (EHV-1) efficiently entered and replicated in CHO-K1 cells that lack the entry receptors HveA, HveB, and HveC, demonstrating that EHV-1 utilizes a unique entry receptor. As with other alphaherpesviruses, efficient EHV-1 entry was dependent on glycoprotein D and cell surface glycosaminoglycans.
TEXT
Equine herpesvirus 1 (EHV-1), a member of the Alphaherpesvirus subfamily, is the causative agent of respiratory distress, abortion, and neurological disease in horses (1). Although many aspects of the virus life cycle have been very well characterized (15), the early events in virus attachment and entry have not been systematically investigated. In particular, while entry receptors for several other alphaherpesviruses, including herpes simplex virus type 1 and 2 (HSV-1 and HSV-2), pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1) have been identified, the ability of EHV-1 to use the same or different entry receptors is unknown.
HveA is a member of the tumor necrosis factor (TNF) receptor family and mediates entry of HSV-1 and HSV-2, but not PRV or BHV-1 (11). HveC (nectin 1) belongs to the immunoglobulin superfamily and mediates entry of all of these alphaherpesviruses (6). HveB, another immunoglobulin superfamily member, is also a receptor for PRV, HSV-2, and the Rid1 variant of HSV-1 (22). In addition to HveA, HveB, and HveC, a modified form of heparan sulfate, 3-O-sulfated heparan sulfate, can mediate the entry of HSV-1 (17). All of the receptors are recognized by glycoprotein D (gD) that in turn initiates the entry process (3, 7-9, 23).
While a specific entry receptor has yet to be characterized for EHV-1, studies have shown that EHV-1 uses the same subset of viral glycoproteins utilized by other alphaherpesviruses for binding and entry into permissive cells. Similar to HSV-1, positively charged residues in EHV-1 gB and gC bind to heparan sulfate (HS) moieties on the cell surface (16, 19). After initial attachment, EHV-1 gD is required for virus entry, but no description of its putative cognate receptor has been reported. In addition to gD, gB is also essential for virus penetration, growth, and cell-to-cell spread (13). gH and gL are essential for HSV-1 and HSV-2 entry (12, 18, 20), but whether these glycoproteins play a similar role in the EHV-1 entry pathway is unknown.
The aim of this study was to ascertain whether EHV-1 utilizes the same or novel entry receptor(s) compared with other well-characterized alphaherpesviruses. To this end, the infectivity of EHV-1 on a panel of cell lines that express different virus receptors was compared to the known infectivity patterns of other alphaherpesviruses. These cell lines included HSV-1- permissive cells CHO-A (HveA), CHO-C (HveC), and Vero, EHV-1-permissive rabbit kidney cell line RK13, and HSV-1-resistant cell lines CHO-K1 and J1.1-2.
CHO-K1, CHO-A, CHO-C, RK13, and Vero cells were infected with a recombinant EHV-1 (L11gIgE), derived from the RacL11 strain, that expresses lacZ (5), and the cells were stained with 5-bromo-4-chloro-3-indolyl-?-D-galactopyranoside (X-Gal) 7 h postinfection (p.i.) to assess entry. L11gIgE efficiently entered RK13, CHO-K1, CHO-A, and CHO-C cells but exhibited severely impaired entry into Vero cells (Fig. 1A). In contrast, an HSV-1 recombinant that expresses lacZ (QOZHG) (2) did not infect CHO-K1 cells but efficiently entered all other cell lines that express at least one of the HSV-1 entry receptors (Fig. 1B). At the same multiplicity of infection (MOI), L11gIgE was further shown to enter another HSV-resistant cell line, J1.1-2 (Fig. 1C), as well as HSV-1-resistant CHO-B (HveB) cells (data not shown). An EHV-1 recombinant derived from the KyA strain, KyAgp2 (21), also efficiently entered CHO-K1 and J1.1-2 cells (data not shown). These data showed that EHV-1 entry into cells is independent of any of the known alphaherpesvirus receptors. In addition, the ability of two EHV-1 strains to efficiently enter two different HSV-resistant cell lines, CHO-K1 and J1.1-2, suggests a common mechanism for EHV-1 entry into these cells which is not strain specific. However, from these data, it is unclear whether EHV-1 is utilizing one common entry receptor or two different receptors on these cells.
Previous studies by Csellner et al. showed that EHV-1 gD is essential for EHV-1 entry into permissive RK13 cells (4). To examine whether EHV-1 gD is required for entry into HSV receptor-negative cells, CHO-K1 cells were infected with a gD-null virus EHV-1gD (derived from the HVS25A strain) (4). Complemented EHV-1gD was passed through noncomplementing RK13 or EHV-1 gD-expressing RK13 (RKgD) cells, and clarified infected-cell lysates were used to infect CHO-K1, Vero, or RK13 cells. As shown in Fig. 2, gD-complemented virus from RKgD cells [EHV-1gD(gD+)] was able to efficiently enter CHO-K1 and RK13 cells, while only a few lacZ+ cells were observed on infection with noncomplemented virus [EHV-1gD(gD–)]. These data supported the conclusion that gD is required for efficient entry of EHV-1 into HSV receptor-negative cells.
In addition to gD, efficient EHV-1 entry also required the expression of glycosaminoglycans (GAGs), since CHO-K1 cells deficient in GAG synthesis (pgsA745) (10) were poorly infected with EHV-1 after a 2-h attachment phase (Fig. 3). However, the presence of cell surface GAGs was not sufficient for entry, since GAG-expressing Vero cells were highly resistant to EHV-1 infection. Entry of EHV-1 into CHO-K1 cells occurred rapidly, and the kinetics of EHV-1 entry into CHO-K1 cells were similar to that of EHV-1 on the standard permissive host cell line, RK13 (Fig. 3). These data corroborate previous work showing that GAG receptor binding is essential for efficient alphaherpesvirus entry (16, 18, 19).
To assay the ability of EHV-1 to replicate in CHO cells, a one-step growth assay was performed. CHO-K1, CHO-A, CHO-C, Vero, or RK13 cells were infected with L11gIgE at an MOI of 1 (Fig. 4). Cells were washed with acidic buffer at 2 h p.i., and the titers of supernatants harvested at various time points were determined in RK13 cells. At 8 h p.i., the virus titers were similar for CHO-K1, CHO-A, and CHO-C cells, while the titers in Vero cells were reduced 533-fold compared to those in CHO-K1 cells. The reduced titers in Vero cells at early time points corresponded with the decreased entry kinetics of EHV-1 in Vero cells (Fig. 3); however, there was no postentry block to replication after EHV-1 entry in these cells. EHV-1 titers in RK13 cells reached a maximum of 3.27 x 107 PFU/ml at 48 h p.i. Compared to EHV-1 titers in RK13 cells, EHV-1 titers in CHO-K1 cells were reduced 72-fold, reaching a maximum of 4.53 x 105 PFU/ml at 48 h p.i. The maximum titers in Vero cells were reduced 744-fold compared to titers in RK13 cells and were reduced 10-fold compared to titers in CHO-K1 cells. These data show that EHV-1 can productively replicate and produce progeny virus in CHO-K1 cells.
Interestingly, PRV and HSV-2 were previously shown to enter CHO-K1 cells (14, 24). However, entry into these cells was greatly enhanced when one of the alphaherpesvirus receptors was expressed (6, 14). Future studies will examine whether the entry receptor utilized by EHV-1 on CHO-K1 cells is similar or distinct from the receptor(s) recognized by HSV-2 and PRV.
In summary, EHV-1 entry is mediated by an uncharacterized receptor that is distinct from all of the previously identified alphaherpesvirus receptors. EHV-1 entry into HSV-resistant cells is dependent upon gD expression, and entry is greatly enhanced in cells that express GAGs. Current experiments are aimed at identifying the EHV-1 entry receptor or receptors.
ACKNOWLEDGMENTS
We thank Millar Whalley for generously providing the EHV-1gD virus and the complementing RKgD cell line. We thank Patricia Spear for generously providing the CHO-A, CHO-B, and CHO-C cell lines. We thank Gabriella Campadelli-Fiume for kindly providing the J1.1-2 cells.
This work was supported in part by a Program of Excellence in Gene Therapy grant (HL66949-01) from NIH/NHLBI, an R01 grant (NS044323) from NIH, and grants AI22001 and P20-RR018724 from NIH.
REFERENCES
Allen, G. P., and J. T. Bryans. 1986. Molecular epizootiology, pathogenesis, and prophylaxis of equine herpesvirus-1 infections. Prog. Vet. Microbiol. Immunol. 2:78-144.
Chen, X., J. Li, M. Mata, J. Goss, D. Wolfe, J. C. Glorioso, and D. J. Fink. 2000. Herpes simplex virus type 1 ICP0 protein does not accumulate in the nucleus of primary neurons in culture. J. Virol. 74:10132-10141.
Cocchi, F., M. Lopez, L. Menotti, M. Aoubala, P. Dubreuil, and G. Campadelli-Fiume. 1998. The V domain of herpesvirus Ig-like receptor (HIgR) contains a major functional region in herpes simplex virus-1 entry into cells and interacts physically with the viral glycoprotein D. Proc. Natl. Acad. Sci. USA 95:15700-15705.
Csellner, H., C. Walker, J. E. Wellington, L. E. McLure, D. N. Love, and J. M. Whalley. 2000. EHV-1 glycoprotein D (EHV-1 gD) is required for virus entry and cell-cell fusion, and an EHV-1 gD deletion mutant induces a protective immune response in mice. Arch. Virol. 145:2371-2385.
Frampton, A. R., Jr., P. M. Smith, Y. Zhang, T. Matsumura, N. Osterrieder, and D. J. O'Callaghan. 2002. Contribution of gene products encoded within the unique short segment of equine herpesvirus 1 to virulence in a murine model. Virus Res. 90:287-301.
Geraghty, R. J., C. Krummenacher, G. H. Cohen, R. J. Eisenberg, and P. G. Spear. 1998. Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 280:1618-1620.
Johnson, D. C., and M. W. Ligas. 1988. Herpes simplex viruses lacking glycoprotein D are unable to inhibit virus penetration: quantitative evidence for virus-specific cell surface receptors. J. Virol. 62:4605-4612.
Johnson, R. M., and P. G. Spear. 1989. Herpes simplex virus glycoprotein D mediates interference with herpes simplex virus infection. J. Virol. 63:819-827.
Krummenacher, C., A. V. Nicola, J. C. Whitbeck, H. Lou, W. Hou, J. D. Lambris, R. J. Geraghty, P. G. Spear, G. H. Cohen, and R. J. Eisenberg. 1998. Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry. J. Virol. 72:7064-7074.
Lidholt, K., J. L. Weinke, C. S. Kiser, F. N. Lugemwa, K. J. Bame, S. Cheifetz, J. Massague, U. Lindahl, and J. D. Esko. 1992. A single mutation affects both N-acetylglucosaminyltransferase and glucuronosyltransferase activities in a Chinese hamster ovary cell mutant defective in heparan sulfate biosynthesis. Proc. Natl. Acad. Sci. USA 89:2267-2271.
Montgomery, R. I., M. S. Warner, B. J. Lum, and P. G. Spear. 1996. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell 87:427-436.
Muggeridge, M. I. 2000. Characterization of cell-cell fusion mediated by herpes simplex virus 2 glycoproteins gB, gD, gH and gL in transfected cells. J. Gen. Virol. 81:2017-2027.
Neubauer, A., B. Braun, C. Brandmuller, O. R. Kaaden, and N. Osterrieder. 1997. Analysis of the contributions of the equine herpesvirus 1 glycoprotein gB homolog to virus entry and direct cell-to-cell spread. Virology 227:281-294.
Nixdorf, R., J. Schmidt, A. Karger, and T. C. Mettenleiter. 1999. Infection of Chinese hamster ovary cells by pseudorabies virus. J. Virol. 73:8019-8026.
O'Callaghan, D. J., and N. Osterrieder. 1999. The equine herpesviruses, p. 508-515. In R.G. Webster and A. Granoff (ed.), Encyclopedia of virology. Harcourt Brace, San Diego, Calif.
Osterrieder, N. 1999. Construction and characterization of an equine herpesvirus 1 glycoprotein C negative mutant. Virus Res. 59:165-177.
Shukla, D., J. Liu, P. Blaiklock, N. W. Shworak, X. Bai, J. D. Esko, G. H. Cohen, R. J. Eisenberg, R. D. Rosenberg, and P. G. Spear. 1999. A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 99:13-22.
Spear, P. G. 1993. Entry of alphaherpesviruses into cells. Semin. Virol. 4:167-180.
Sugahara, Y., T. Matsumura, Y. Kono, E. Honda, H. Kida, and K. Okazaki. 1997. Adaptation of equine herpesvirus 1 to unnatural host led to mutation of the gC resulting in increased susceptibility of the virus to heparin. Arch. Virol. 142:1849-1856.
Turner, A., B. Bruun, T. Minson, and H. Browne. 1998. Glycoproteins gB, gD, and gHgL of herpes simplex virus type 1 are necessary and sufficient to mediate membrane fusion in a Cos cell transfection system. J. Virol. 72:873-875.
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