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Glycoprotein C of herpes simplex virus type 1 prevents complement-mediated cell lysis and virus neutralization
1Department of Medicine, University of Pennsylvania, Philadelphia 19104.
Insights
Herpes simplex virus type 1 glycoprotein gC1 protects against complement-mediated damage. This glycoprotein (gC1) blocks complement activation on infected cells and neutralizes viruses, highlighting its protective role.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Herpes simplex virus type 1 (HSV-1) utilizes surface glycoproteins for host interactions.
- Complement component C3b is a key molecule in the complement system, involved in pathogen clearance and inflammation.
- Glycoprotein gC1 of HSV-1 is known to bind C3b, but its functional role in complement interactions is not fully understood.
Purpose of the Study:
- To investigate the role of HSV-1 glycoprotein gC1 in modulating complement interactions with infected cells and cell-free virus.
- To determine if gC1 confers protection against complement-mediated lysis and neutralization.
Main Methods:
- Comparison of wild-type HSV-1 (NS) with a gC1-deficient mutant (ns-1) in terms of susceptibility to complement-mediated cytolysis.
- Expression of gC1 and gD1 genes in mammalian cells using an inducible promoter system.
- Assessment of complement pathway activation (alternative and classical) in the presence and absence of gC1.
Main Results:
- Cells infected with the gC1 mutant (ns-1) were significantly more susceptible to complement-mediated antibody-dependent and independent cytolysis compared to wild-type infected cells.
- Mammalian cells induced to express gC1 demonstrated resistance to complement-mediated cytolysis, whereas cells expressing gD1 did not.
- gC1 was found to inhibit alternative complement pathway activation on infected/transfected cells.
- gC1 also inhibited complement-dependent virus neutralization by interfering with the classical complement pathway.
Conclusions:
- Glycoprotein gC1 plays a crucial protective role for HSV-1, both on the virion surface and on infected cells.
- gC1 actively modulates the host complement system, preventing both cell lysis and virus neutralization.
- These findings elucidate a key immune evasion mechanism employed by HSV-1.
Abstract:
Glycoprotein gC1 of herpes simplex virus type 1 (HSV-1) binds complement component C3b. To determine if gC1 modifies the interaction of complement with virus-infected cells or cell-free virus, ns-1, a mutant HSV-1 strain that does not express gC1 at the cell surface and does not bind C3b, was compared with its parental strain, NS. Cells infected with the gC1 mutant were more susceptible to cytolysis mediated by antibody and complement or complement alone. The gC1 or gD1 genes were expressed in mammalian cells under the control of an inducible promoter. Cells induced to express gC1 resisted complement cytolysis, while cells expressing gD1 did not. gC1 modified cytolysis of virus-infected or -transfected cells by blocking alternative complement pathway activation. gC1 also modified complement-dependent virus neutralization, which was mediated by inhibiting the classical complement pathway. These results indicate a protective role for gC1 on the virion and at the cell surface.