Characterization of glycoprotein C-negative mutants of herpes simplex virus type 1 isolated from a patient with keratitis

Hidaka, Yoshiki; Sakuma, Shunji; Kumano, Yuji; Minagawa, Hiroko; Mori, Ryoichi

doi:10.1007/bf01316673

Cited by 30 publications

(24 citation statements)

References 27 publications

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“…We now report that complement has no effect on the blocking virus attachment or on aggregating gC null virus; therefore, the mechanisms by which complement neutralizes HSV-1 gC null virus differ from those reported for other viruses either in the presence or absence of specific Abs. The fact that gC inhibits complement neutralization helps explain why gC is conserved in viruses isolated from clinical samples (51,52), with rare exception (53), despite the finding that gC is nonessential for virus replication in vitro (54). gC promotes virus attachment to cells by binding to cell surface heparan sulfate (55,56).…”

Section: Discussionmentioning

confidence: 99%

Novel Mechanism of Antibody-Independent Complement Neutralization of Herpes Simplex Virus Type 1

Friedman¹,

Wang²,

Pangburn

et al. 2000

The Journal of Immunology

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The envelope surface glycoprotein C (gC) of HSV-1 interferes with the complement cascade by binding C3 and activation products C3b, iC3b, and C3c, and by blocking the interaction of C5 and properdin with C3b. Wild-type HSV-1 is resistant to Ab-independent complement neutralization; however, HSV-1 mutant virus lacking gC is highly susceptible to complement resulting in ≥100-fold reduction in virus titer. We evaluated the mechanisms by which complement inhibits HSV-1 gC null virus to better understand how gC protects against complement-mediated neutralization. C8-depleted serum prepared from an HSV-1 and -2 Ab-negative donor neutralized gC null virus comparable to complement-intact serum, indicating that C8 and terminal lytic activity are not required. In contrast, C5-depleted serum from the same donor failed to neutralize gC null virus, supporting a requirement for C5. EDTA-treated serum did not neutralize gC null virus, indicating that complement activation is required. Factor D-depleted and C6-depleted sera neutralized virus, suggesting that the alternative complement pathway and complement components beyond C5 are not required. Complement did not aggregate virus or block attachment to cells. However, complement inhibited infection before early viral gene expression, indicating that complement affects one or more of the following steps in virus replication: virus entry, uncoating, DNA transport to the nucleus, or immediate early gene expression. Therefore, in the absence of gC, HSV-1 is readily inhibited by complement by a C5-dependent mechanism that does not require viral lysis, aggregation, or blocking virus attachment.

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Section: Discussionmentioning

confidence: 99%

Novel Mechanism of Antibody-Independent Complement Neutralization of Herpes Simplex Virus Type 1

Friedman¹,

Wang²,

Pangburn

et al. 2000

The Journal of Immunology

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“…Most of the fresh isolates of HSV-1 maintained the ability to produce gC, except for a very few cases of gCnegative mutants (7). It is generally believed that gCpositive strains have some advantages over gC-negative strains in in vivo environments.…”

Section: Resultsmentioning

confidence: 99%

In Vitro Selection of Variants of Herpes Simplex Virus Type 1 Which Differ in Cytopathic Changes

Padilla

Yamada

Tsukazaki

et al. 1997

Microbiology and Immunology

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To analyze the mechanisms for in vitro emergence of the syncytial variants of herpes simplex virus type 1 (HSV‐1), several cell lines were infected with a mixture of equal amounts of two HSV‐1 variants, one syncytial and the other non‐syncytial, and changes in their relative abundance were monitored during passage. With a combination of two variants of the Miyama strain of HSV‐1, the syncytial variant became dominant during passage in Vero, RK‐13 and FL cells. On the other hand, the ratios of the two variants remained around 1:1 during the passage in HEp‐2, MGC and HEL cells. In another set of variants of the SKO strain of HSV‐1, the outcomes were different from those of the Miyama strain in the FL, MGC and HEp‐2 cells. The ratios of the two variants remained around 1:1 during passage in FL cells, while the non‐syncytial variant became dominant during passage in MGC and HEp‐2 cells. In addition, we examined the effects of a complement and interferon‐β (IFN‐β) on the outcome of the selection. As a result, the complement slowed the selection of a syncytial variant, whereas IFN‐β facilitated it.

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“…Vero cells grown in Eagle's MEM supplemented with 5 ~ calf serum were used for virus propagation, titration and transfection. The virus strains used were HSV-1 strain KOS, a laboratory strain of HSV-t ; HSV-1 gC-mutant strain TN1, a clinical isolate from human keratitis (Hidaka et al, 1990) and C-1 to C-5, recombinant HSV-1 viruses obtained in this study.…”

Section: Methodsmentioning

confidence: 99%

“…We previously reported very rare gC-mutants (strains TN1, TN2 and TN3) isolated from a patient with recurrent keratitis (Hidaka et al, 1990). In the present study, we used the clinical gC-isolates to investigate the interaction between gC and complement in the absence of antibody.…”

Section: Introductionmentioning

confidence: 99%

Glycoprotein C of herpes simplex virus type 1 is essential for the virus to evade antibody-independent complement-mediated virus inactivation and lysis of virus-infected cells

Hidaka

Sakai

Toh

et al. 1991

Journal of General Virology

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Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) is a receptor for the complement component C3b. We have previously isolated HSV-1 gC-strains (TN1, TN2 and TN3) from a patient with recurrent keratitis at three different times. These are very rare isolates because gC was thought to be essential for the virus in vivo. To determine whether gC modifies the interaction of complement with cell-free virus or virusinfected cells, we constructed gC + recombinant viruses in which the intact gC gene of strain KOS was inserted into the TN 1 virus genome. TN 1 virus was inactivated by complement and TN1 virus-infected cells were lysed by complement; however, gC ÷ recombinant viruses became resistant to these effects of complement. These results suggest a role for gC in protection of both the virion envelope and the infected cell surface against damage by complement. TN1 virus was inactivated by complement from rats (Wistar, WKA, F344 and SD), guinea-pigs (Hartley) and humans, but not by complement from mice (C3H, DDD and BALB/c), which indicates that mice seem to be inappropriate as an experimental model for the study of HSV infection in which complement factors need to be considered.

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Characterization of glycoprotein C-negative mutants of herpes simplex virus type 1 isolated from a patient with keratitis

Cited by 30 publications

References 27 publications

Novel Mechanism of Antibody-Independent Complement Neutralization of Herpes Simplex Virus Type 1

Novel Mechanism of Antibody-Independent Complement Neutralization of Herpes Simplex Virus Type 1

In Vitro Selection of Variants of Herpes Simplex Virus Type 1 Which Differ in Cytopathic Changes

Glycoprotein C of herpes simplex virus type 1 is essential for the virus to evade antibody-independent complement-mediated virus inactivation and lysis of virus-infected cells

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