Variations in autologous neutralization and CD4 dependence of b12 resistant HIV-1 clade C env clones obtained at different time points from antiretroviral naïve Indian patients with recent infection.
BACKGROUND
Limited information is available on HIV-1 Indian clade C sensitivities to autologous antibodies during the course of natural infection. In the present study, a total of 37 complete envelope clones (Env) were amplified at different time points predominantly from the plasma of five Indian patients with recent HIV-1 infection and envelope-pseudotyped viruses were examined for their magnitude of sensitivity to autologous plasma antibodies during natural course of infection.


RESULTS
Variable low levels of neutralization were consistently detected with contemporaneous autologous plasma. In contrast to clade B and African clade C HIV-1 envelopes, Env clones obtained from four patients were found to be resistant to IgG1b12. The majority of the Env clones were resistant to 2G12 and 2F5 due to the absence of the minimal motifs required for antibody recognition, but were sensitive to 4E10. Nonetheless, Env clones from one patient were found to be sensitive to 2G12, atypical for clade C, and one Env clone exhibited unusual sensitivity to 17b, suggesting spontaneous exposure of CD4i epitopes. Phylogenetic analysis revealed that Env clones were closely clustered within patients. Variation in the potential N-linked glycosylation pattern also appeared to be different in patients over the course of infection. Interestingly, we found that the sensitivity of Envs to contemporaneous autologous NAbs correlated positively with increased sensitivity to soluble CD4 and inversely with anti-CD4 antibody and Envs with increased NAb sensitivity were able to efficiently infect HeLa cells expressing low CD4.


CONCLUSIONS
Our data showed considerable variations in autologous neutralization of these early HIV-1 clade C Envs in each of these patients and indicate greater exposure to CD4 of Envs that showed increased autologous neutralization. Interestingly, Env clones obtained from a single patient at different time points were found to retain sensitivity to b12 antibody that binds to CD4 binding site in Env in contrast to Envs obtained from other patients. However, we did not find any association between increased b12 sensitivity of Envs obtained from this particular patient with their degree of exposure to CD4.
Ringe
Rajesh
R
Department of Molecular Virology, National AIDS Research Institute, Indian Council of Medical Research, G-73 MIDC, Bhosari, Pune, India.
Thakar
Madhuri
M
Bhattacharya
Jayanta
J
D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000918:Antibody Specificity; D000080908:Broadly Neutralizing Antibodies; D015704:CD4 Antigens / Q000378:metabolism*; D024882:Drug Resistance, Viral; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007194:India; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
C529157:2G12 monoclonal antibody; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; D015704:CD4 Antigens; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus