title: The role of viral fitness in HIV pathogenesis.
abstract: The development of clinical symptoms, and clinical progression among persons infected with HIV-1 is the manifestation of the effects of the pathogenic viral life cycle of HIV-1. Individual variants of HIV-1 vary widely in features that determine viral fitness and virulence. HIV-1 exploits host antiviral responses, the APOBEC3G cytidine deaminase, and the low-fidelity HIV-1 reverse transcriptase, to ensure new variants with novel phenotypic features are continually present for expansion in response to changing conditions in the host, such as immune responses, or antiretroviral therapy. This high-level variance has led to a wide range in observed fitness and virulence, across strains of HIV-1. The HIV-1 pol replication capacity assay (pol RC) measures features of viral fitness, associates with elevated CD4+ T-cell counts, yet is not strongly associated with HIV-1 RNA levels. The biological basis for elevated CD4+ T-cell counts among those carrying a virus of low pol RC may be because of lowered virus infectivity, or restricted tissue replication.
authors.affiliation: Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Barbour
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
mesh_terms: D000071480:APOBEC-3G Deaminase; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003564:Cytidine Deaminase; D015658:HIV Infections / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D015497:HIV-1 / Q000201:enzymology / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D009700:Nucleoside Deaminases; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D012097:Repressor Proteins; D014779:Virus Replication / Q000276:immunology
chemical_list: D011506:Proteins; D012097:Repressor Proteins; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase