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Vaccinia Reporter Viruses for Quantifying Viral Function at All Stages of Gene Expression
Published on: May 15, 2014
The Vaccinia virus complement control protein modulates adaptive immune responses during infection
Natasha M Girgis1, Brian C Dehaven, Yuhong Xiao
1University of Pennsylvania School of Medicine, Division of Infectious Diseases, 502 Johnson Pavilion, Philadelphia, PA 19104-6073, USA.
Journal of Virology
|December 31, 2010
Summary
Vaccinia virus complement control protein (VCP) dampens anti-viral immune responses. Inhibiting VCP in vaccinia virus enhances T cell and antibody responses, reducing viral virulence.
Area of Science:
- Immunology
- Virology
- Infectious Disease
Background:
- Complement activation is crucial for innate and adaptive immunity against viruses.
- Pathogen-encoded complement inhibitors can impact immune responses, but their mechanisms are often unclear.
- Vaccinia virus complement control protein (VCP) is a known virulence factor, but its precise role in modulating adaptive immunity is undefined.
Purpose of the Study:
- To investigate how vaccinia virus complement control protein (VCP) influences anti-viral T cell and antibody responses.
- To determine the role of VCP in vaccinia virus pathogenesis by comparing wild-type and VCP-deficient viruses.
- To elucidate the mechanisms by which VCP contributes to viral virulence.
Main Methods:
- Comparison of wild-type vaccinia virus (vv-VCPwt) and VCP-deficient vaccinia virus (vv-VCPko) in an intradermal mouse infection model.
- Assessment of lesion size, immune cell infiltration (T cells), antibody production, and viral titers.
- Experimental depletion of CD8(+) and CD4(+) T cells to evaluate their role in VCP-mediated virulence.
Main Results:
- VCP-deficient vaccinia virus (vv-VCPko) produced smaller lesions in wild-type mice, but not in complement-deficient mice, indicating VCP's role in virulence.
- Attenuation of vv-VCPko correlated with increased T cell accumulation, enhanced neutralizing antibody responses, and lower viral loads.
- Depletion of both CD8(+) and CD4(+) T cells restored the virulence of vv-VCPko to wild-type levels, highlighting the importance of T cell-mediated immunity.
Conclusions:
- Vaccinia virus complement control protein (VCP) contributes to viral virulence by suppressing anti-viral T cell and antibody responses.
- Pathogen-encoded complement regulatory proteins can significantly modulate adaptive immunity during viral infections.
- Targeting VCP or complement regulation pathways could be a strategy to enhance anti-viral immunity.
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