title: HIV-1 clade C envelopes obtained from late stage symptomatic Indian patients varied in their ability towards relative CD4 usages and sensitivity to CCR5 antagonist TAK-779.
abstract: The mechanism by which strictly CCR5 using HIV-1 clade C variants exacerbate disease progression in absence of coreceptor switch is not clearly known. We previously reported HIV-1 clade C envelopes (Env) obtained from late stage Indian patients with expanded coreceptor tropism. Here we compared such Envs (having expanded coreceptor tropism) with strictly CCR5 using Envs also obtained from late stage in their capacity to utilize CD4 and CCR5 for productive entry. We found that while envelopes with low CD4 dependence tend to infect primary CD4(+) T cells better than those required optimum CD4 for entry, no significant association was found between low CD4 usage and infectivity of primary CD4(+) T cells by Env-pseudotyped viruses and their sensitivity to CCR5 antagonist TAK-779. Interestingly, Envs that readily infected HeLa cells expressing low CD4 showed relative resistance to T20 indicating that conformational intermediates of these envelopes remained for a shorter period of time than is required for efficient inhibition by T20.
authors.affiliation: Department of Molecular Virology, National AIDS Research Institute, G-73 MIDC, Bhosari, Pune 411026, India.
authors.forename: Lavina
authors.initials: L
authors.lastname: Gharu
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ringe
authors.forename: Jayanta
authors.initials: J
authors.lastname: Bhattacharya
mesh_terms: D000577:Amides / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology; D015704:CD4 Antigens / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D007194:India; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011485:Protein Binding; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D053586:Virus Internalization; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D015704:CD4 Antigens; D000644:Quaternary Ammonium Compounds; D019713:Receptors, CCR5; D015728:Receptors, HIV; D054299:env Gene Products, Human Immunodeficiency Virus; C119369:TAK 779