Localization on the herpes simplex virus type 1 genome of a region encoding proteins involved in adsorption to the cellular receptor

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274

The purpose of this study was to identify the herpes simplex virus glycoprotein(s) that mediates the adsorption of virions to cells. Because heparan sulfate moieties of cell surface proteoglycans serve as the receptors for herpes simplex virus adsorption, we tested whether any of the viral glycoproteins could bind to heparin-Sepharose in affinity chromatography experiments. Two glycoproteins, gB and gC, bound to heparin-Sepharose and could be eluted with soluble heparin. In order to determine whether virions devoid of gC or gB were impaired for adsorption, we quantitated the binding of wild-type and mutant virions to cells. We found that at equivalent input concentrations of purified virions, significantly fewer gC-negative virions bound to cells than did wild-type or gB-negative virions. In addition, the gC-negative virions that bound to cells showed a significant delay in penetration compared with wild-type virus. The impairments in adsorption and penetration of the gC-negative virions can account for their reduced PFU/particle ratios, which were found to be about 5 to 10% that of wild-type virions, depending on the host cell. Although gC is dispensable for replication of herpes simplex virus in cell culture, it clearly facilitates virion adsorption and enhances infectivity by about a factor of 10.

Section: Discussionmentioning

confidence: 93%

Glycoprotein C of herpes simplex virus type 1 plays a principal role in the adsorption of virus to cells and in infectivity

Herold

WuDunn

Soltys

et al. 1991

510

274

“…In so far as these experiments use whole virions as competitors, it is difficult to draw conclusions regarding the nature of the interference. Using another approach, it has been shown that neomycin and polylysine can inhibit HSV-1 but not HSV-2 infection of BHK cells (22)(23)(24). Neomycin inhibits HSV-1 infection by competing with gC-1 for binding heparan sulfate glycosaminoglycans, which suggests that gC-1 and gC-2 recognize different moieties on cell surface heparan sulfate (16).…”

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confidence: 99%

Dextran sulfate can act as an artificial receptor to mediate a type-specific herpes simplex virus infection via glycoprotein B

Dyer

Banfield

Martindale

et al. 1997

Herpes simplex virus (HSV) adsorption to host cells is mediated, at least in part, by the interaction of viral glycoproteins with cell surface glycosaminoglycans such as heparan sulfate and chondroitin sulfate. To investigate the contribution of various cell surface components in the infection pathway, we isolated a mutant cell line, sog9, which is unable to synthesize glycosaminoglycans (B. W. Banfield, Y. Leduc, L. Esford, K. Schubert, and F. Tufaro, J. Virol. 69:3290-3298, 1995). Although HSV-1 and HSV-2 infection of sog9 cells is diminished, the cells are still infected at about 0.5% efficiency, which suggests that these cells normally express at least one nonglycosaminoglycan receptor. In this report, we used sog9 cells to test whether glycosaminoglycan analogs, such as dextran sulfate (DS), could functionally substitute for cellular glycosaminoglycans to initiate HSV infection. We show that high-molecular-weight DS added either prior to or during inoculation stimulated HSV-1 but not HSV-2 infection by up to 35-fold; DS added after viral adsorption had no effect on infection efficiency. Moreover, DS stimulated HSV-1 infection at 4؇C, indicating that this compound impinged on an early, energy-independent step in infection. Using radiolabeled virus, we showed that HSV-1 is more efficient than HSV-2 in adsorbing to DS immobilized on microtiter wells. This raised the possibility that only HSV-1 could engage additional receptors to initiate infection in the presence of DS. To determine which viral component(s) facilitated DS stimulation, a panel of intertypic recombinants and deletion mutant viruses was investigated. These assays showed that DS stimulation of infection is mediated primarily by gB-1. Thus, this study provides direct evidence that a principal role for cell surface glycosaminoglycans in HSV infection is to provide an efficient matrix for virus adsorption. Moreover, by using DS as an alternative adsorption matrix (a trans receptor), we uncovered a functional, type-specific interaction of HSV-1 with a cell surface receptor.

“…For herpes simplex virus type 1 (HSV-1), studies involving antibody inhibition (7), virosomes (12), and cell membrane fractionation (13) have indicated that this virus uses envelope glycoproteins, including glycoprotein B (gB), gC, and gD, as the major VAPs. However, since gC is dispensible for virus growth in cell culture, the role played by this protein as a VAP has been questioned (11,16). In addition, even though gB and gD are not dispensable, gB-and gDmutants are still able to bind to permissive cells (3, 10), suggesting that they may not be required for attachment.…”

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confidence: 99%

“…Recently, it was reported that the cellular receptor of HSV-1 contains a heparinlike component (32), and the interactions between HSV-1 but not HSV-2 and permissive cells could be interrupted by polycationic compounds, including neomycin (14)(15)(16). By making intertypic recombinants between HSV-1 and HSV-2, the gene(s) coding for the viral component(s) responsible for the neomycin effect was mapped to a region of the HSV-1 genome that encoded the gC gene (16). However, since an HSV-1 gCmutant was still sensitive to neomycin, and since no other glycoprotein gene is located near the gC gene, the authors suggested that a nonglycosylated protein encoded by a gene near the gC locus may be the HSV-1 VAP (16).…”

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confidence: 99%

“…Effect of neomycin on adsorption. Neomycin has been previously shown to inhibit HSV-1 infection by interacting with host cell receptors, thereby preventing their recognition by the virus (14)(15)(16). Therefore, during the characterization of the BHV-1 gIlmutant, we tested the effect of neomycin on adsorption for both the wt and gIIIviruses, anticipating that the drug might have a preferential inhibitory effect on Hughes et al (8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Bovine herpesvirus 1 attachment to permissive cells is mediated by its major glycoproteins gI, gIII, and gIV

Liang

Babiuk

Hurk

et al. 1991

A bovine herpesvirus 1 (BHV-1) gIII deletion mutant (gIII-) was produced by means of recombinant DNA that retained the ability to replicate in cell culture. However, the gIllmutant was functionally defective, showing impaired attachment to permissive cells, a delay in virus replication, and reduced extracellular virus production. The attachment defect exhibited by the gIlmutant is an indication of the role played by glll in the normal infection process. This was shown by dramatically decreased binding of radiolabelled glllvirus to permissive cells and a slower adsorption rate, as measured by plaque formation, than the wild-type (wt) virus. Furthermore, treatment of the glllvirus with neomycin increased virus adsorption and plaque formation by severalfold, whereas neomycin treatment had no effect on the wt virus. This observation showed that the glllmutant was strictly defective in adsorption but fully competent to produce productive infections once induced to attach. The glllmutant showed greater sensitivities than did the wt virus to anti-gI and anti-gIV antibody-mediated neutralization. Analyses with panels of monoclonal antibodies to gI and gIV revealed that the epitopes gI-IV and gIV-III were the main targets for enhanced neutralization. This provided evidence that gI and gIV may also participate in virus attachment. Finally, when affinity-purified gI, glll, and gIV were tested for their ability to inhibit virus adsorption, gIlI had the most pronounced inhibitory effect, followed by gI and then gIV. glll was able to completely inhibit wt virus adsorption, and at a high concentration, it also partially inhibited the glllmutant. gI and gIV inhibited wt and glllmutant adsorption to a comparable extent. Our results collectively indicate that glll plays a predominant role in virus attachment, but gI and gIV also contribute to this process. In addition, a potential cooperative mechanism for virus attachment with these three proteins is presented.