unique c2v3 sequence in hiv-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization独特c2v3序列在hiv - 1信封里获得广泛中和等离子的缓慢进展患者授予增强病毒中和.pdfVIP
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unique c2v3 sequence in hiv-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization独特c2v3序列在hiv - 1信封里获得广泛中和等离子的缓慢进展患者授予增强病毒中和
Unique C2V3 Sequence in HIV-1 Envelope Obtained from
Broadly Neutralizing Plasma of a Slow Progressing
Patient Conferred Enhanced Virus Neutralization
1 1¤ 1 1 1
Rajesh Ringe , Lipsa Das , Ipsita Choudhary , Deepak Sharma , Ramesh Paranjape , Virander
2 1
Singh Chauhan , Jayanta Bhattacharya *
1 Department of Molecular Virology, National AIDS Research Institute, Pune, India, 2 International Center for Genetic Engineering and Biotechnology, New Delhi, India
Abstract
Broadly neutralizing antibodies to HIV-1 usually develops in chronic infections. Here, we examined the basis of enhanced
¨
sensitivity of an env clone amplified from cross neutralizing plasma of an antiretroviral naıve chronically infected Indian
patient (ID50 .600-fold higher compared to other autologous env clones). The enhanced autologous neutralization of
pseudotyped viruses expressing the sensitive envelope (Env) was associated with increased sensitivity to reagents and
monoclonal antibodies targeting distinct sites in Env. Chimeric viruses constructed by swapping fragments of sensitive Env
into resistant Env backbone revealed that the presence of unique residues within C2V3 region of gp120 governed increased
neutralization. The enhanced virus neutralization was also associated with low CD4 dependence as well as increased
binding of Env trimers to IgG1b12 and CD4-IgG2 and was independent of gp120 shedding. Our data highlighted
vulnerabilities in the Env obtained from cross neutralizing plasma
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