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Mechanisms of resistance of HIV-1 primary isolates to complement-mediated lysis
D M Takefman1, B L Sullivan, B E Sha
1Department of Immunology/Microbiology, Rush University, Chicago, Illinois 60612, USA.
Abstract:
Previous studies suggested that HIV-1 primary isolates (PI) were resistant to complement-mediated lysis (CML), while virus produced in certain T cell lines and virus taken directly from the plasma of HIV+ persons were both susceptible to CML. The purpose of this study was to investigate the mechanism(s) of PI resistance. PI were resistant to CML using pooled seropositive serum as an antibody source. Additionally, PI obtained from two patients at several times over 2 years were resistant to CML using autologous antibody. PI were also resistant to CML induced by monoclonal antibodies which neutralize a broad range of PI. Resistance to CML was associated with low binding of antibody to PI but was not due to low gp120 levels. Cell-line-derived virus and PI were equally sensitive to CML induced by antibody to host-cell proteins, suggesting that PBMC do not contribute properties to virions which make them more physically resistant to CML in general but that PI resistance is restricted to CML induced by antiviral antibody. These studies show that PI are resistant to CML mediated by various antiviral antibodies and indicate that low binding of antibody to virus is an important factor contributing to resistance.
Insights
Human immunodeficiency virus type 1 (HIV-1) primary isolates resist complement-mediated lysis (CML). This resistance is linked to reduced antibody binding, not gp120 levels, highlighting a key factor in viral immune evasion.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Previous studies indicated variable susceptibility of human immunodeficiency virus type 1 (HIV-1) to complement-mediated lysis (CML).
- Virus from T cell lines and patient plasma showed susceptibility, contrasting with resistance observed in primary isolates (PI).
Purpose of the Study:
- To elucidate the underlying mechanisms of HIV-1 primary isolate (PI) resistance to complement-mediated lysis (CML).
Main Methods:
- Assessed PI resistance to CML using pooled seropositive serum, autologous antibodies from patients, and neutralizing monoclonal antibodies.
- Quantified antibody binding to PI and measured gp120 levels.
- Compared CML sensitivity of PI and cell-line-derived virus using antibodies against host-cell proteins.
Main Results:
- HIV-1 primary isolates (PI) demonstrated resistance to CML across various antiviral antibody sources.
- Resistance correlated with significantly lower antibody binding to PI, independent of gp120 expression levels.
- PI and cell-line-derived virus exhibited similar sensitivity to CML induced by anti-host-cell protein antibodies.
Conclusions:
- HIV-1 primary isolates possess a mechanism of resistance to complement-mediated lysis (CML) mediated by diverse antiviral antibodies.
- Reduced antibody binding to the virus is a critical factor contributing to this observed resistance.
- The resistance mechanism appears specific to antiviral antibody-induced CML, not general physical resistance of the virion.