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Journal of Virology, February 2007, p. 1350-1359, Vol. 81, No. 3
0022-538X/07/$08.00+0     doi:10.1128/JVI.01839-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Role of V1V2 and Other Human Immunodeficiency Virus Type 1 Envelope Domains in Resistance to Autologous Neutralization during Clade C Infection

Department of Pathology and Laboratory Medicine,¹ Department of Global Health,² Rollins School of Public Health,³ Department of Medicine,⁴ Division of Infectious Diseases,⁵ Yerkes National Primate Research Center,⁶ Emory Vaccine Center, Emory University, Atlanta, Georgia 30329,⁷ Howard Hughes Medical Institute,⁸ Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294,⁹ Zambia Blood Transfusion Service, Lusaka, Zambia,¹⁰

Received 23 August 2006/ Accepted 18 October 2006

Biologically functional clade C envelope (Env) glycoproteins from the chronically (donor) and newly (recipient) infected partners of four heterosexual transmission pairs in Zambia were cloned and characterized previously. In each case, the donor viral quasispecies contained Envs that were resistant to autologous neutralization by contemporaneous plasma, while the recipient Envs were sensitive to neutralizing antibodies in this donor plasma sample. The donor Envs also varied in length, glycosylation, and amino acid sequence of the V1V2 hypervariable domain of gp120, while the recipient Envs were much more homogeneous. To assess the contribution of V1V2 to the neutralization phenotype of the donor Envs, V1V2 domains from neutralization-sensitive recipient Envs were replaced with donor V1V2 domains, and the autologous neutralization sensitivities of the chimeric Envs were evaluated using a virus-pseudotyping assay. Long donor V1V2 domains regulated sensitivity to autologous neutralization, although the effect was dependent on the Env background. Short donor V1V2 domains did not confer neutralization resistance. Primary sequence differences in V2 were also found to influence neutralization sensitivity in one set of recipient Envs. The results demonstrate that expansion of the V1V2 domain is one pathway to escape from autologous neutralization in subtype C Envs. However, V1V2-independent mechanisms of resistance also exist, suggesting that escape is multifaceted in chronic subtype C infection.

Published ahead of print on 1 November 2006.

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