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Complement control proteins, CD46, CD55, and CD59, as common surface constituents of human and simian
D C Montefiori1, R J Cornell, J Y Zhou
1Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Insights
HIV-1 and SIV viruses utilize complement control proteins CD46, CD55, and CD59 to evade immune detection. These cellular proteins are incorporated into the virus membrane, aiding in complement lysis evasion and potentially impacting vaccine efficacy.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Complement control proteins (CCPs) like CD46, CD55, and CD59 protect host cells from complement-mediated lysis.
- Human Immunodeficiency Virus type 1 (HIV-1) and Simian Immunodeficiency Virus (SIV) are known to acquire cellular proteins, suggesting a potential role in immune evasion.
Purpose of the Study:
- To investigate the presence and role of CCPs (CD46, CD55, CD59) on the surface of HIV-1 and SIV.
- To determine if these CCPs are associated with released virions and contribute to viral immune evasion.
Main Methods:
- Flow cytometry to detect CCP expression on CD4+ cell lines.
- Immunoprecipitation using monoclonal antibodies against CD46, CD55, and CD59 to detect viral association.
- Infectivity assays and p24 core protein release measurements to assess complement-mediated lysis.
Main Results:
- CD46, CD55, and CD59 were found on CD4+ cell lines used for HIV-1 and SIV synthesis.
- These CCPs were physically associated with released HIV-1 and SIV virions, including infectious virus.
- Anti-cell antibodies in macaques, targeting CD46 and CD59, rendered HIV-1 susceptible to complement lysis, reducing infectivity.
Conclusions:
- CD46, CD55, and CD59 are common surface components of HIV-1 and SIV virions.
- These viral-associated CCPs likely contribute to the immune evasion of HIV-1 and SIV.
- The findings suggest that complement-mediated virolysis could be a mechanism underlying SIV vaccine protection mediated by anti-cell antibodies.
Abstract:
Complement control proteins include a group of membrane-bound surface antigens that protect cells from complement lysis by preventing formation of the membrane attack complex (MAC) of complement. HIV-1 and SIV are known to possess cellular proteins, making it possible that some of them contribute to the ability of these viruses to evade complement lysis. Three complement control proteins, CD46 (membrane cofactor protein), CD55 (decay accelerating protein), and CD59 (HRF20), were found by flow cytometry to be expressed on the surface of CD4+ cell lines commonly used for HIV-1 and SIV synthesis. Monoclonal antibodies to each of these proteins precipitated HIV-1 IIIB and SIV delta/B670 synthesized in CEM x 174 cells and two primary HIV-1 isolates synthesized in peripheral blood mononuclear cells, indicating that CD46, CD55, and CD59 are physically associated with the virus membrane after the virus has been released from the surface of infected cells. Additional experiments showed that the precipitated material contained infectious virus, confirming that whole virus was precipitated. Evidence that CD46 and CD59 are immunogenic in macaques was found when anti-cell antibodies in plasmas from macaques immunized with human cell-grown SIV blocked anti-CD46 and anti-CD59 from binding to the surface of CEM x 174 cells. Anti-cell antibodies rendered HIV-1 susceptible to complement lysis as measured by the release of p24 core protein, and consistently produced a complement-dependent reduction in HIV-1 and SIV infectivity of 1-3 logs. These results demonstrate that CD46, CD55, and CD59 are common surface constituents of HIV-1 and SIV. The results also raise the possibility that the mechanism of SIV vaccine protection attributed to anti-cell antibodies could have involved complement-mediated virolysis.