title: Functional characterization of Vif proteins from HIV-1 infected patients with different APOBEC3G haplotypes.
abstract: The human cytidine deaminase APOBEC3G (A3G) potently restricts HIV-1 but the virus, in turn, expresses a Vif protein which degrades A3G. A natural A3G-H186R variant, common in African populations, has been associated with a more rapid AIDS disease progression, but the underlying mechanism remains unknown. We hypothesized that differences in HIV-1 Vif activity towards A3G wild type and A3G-H186R contribute to the distinct clinical AIDS manifestation.
  
  
  
  Vif variants were cloned from plasma samples of 26 South African HIV-1 subtype C infected patients, which either express wild type A3G or A3G-H186R. The Vif alleles were assessed for their ability to counteract A3G variants using western blot and single-cycle infectivity assays.
  
  
  
  We obtained a total of 392 Vif sequences which displayed an amino acid sequence difference of 6.2-19.2% between patients. The intrapatient Vif diversities from patient groups A3G, A3G and A3G were similar. Vif variants obtained from patients expressing A3G and A3G were capable of counteracting both A3G variants with similar efficiency. However, the antiviral activity of A3G-H186R was significantly reduced in both the presence and absence of Vif, indicating that the A3G-H186R variant intrinsically exerts less antiviral activity.
  
  
  
  A3G wild type and A3G-H186R are equally susceptible to counteraction by Vif, regardless of whether the Vif variant was obtained from A3G and A3G patients. However, the A3G-H186R variant intrinsically displayed lower antiviral activity, which could explain the higher plasma viral loads and accelerated disease progression reported for patients expressing A3G.
authors.affiliation: aKwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH) bHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa cDepartment of Microbiology and Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, USA dCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa eRagon Institute of MGH, MIT and Harvard University, Cambridge, Massachusetts, USA fMax Planck Institute for Infection Biology, Chariteplatz, Berlin, Germany. *Kavidha Reddy and Marcel Ooms contributed equally to this work.
authors.forename: Kavidha
authors.initials: K
authors.lastname: Reddy
authors.forename: Marcel
authors.initials: M
authors.lastname: Ooms
authors.forename: Michael
authors.initials: M
authors.lastname: Letko
authors.forename: Nigel
authors.initials: N
authors.lastname: Garrett
authors.forename: Viviana
authors.initials: V
authors.lastname: Simon
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
mesh_terms: D000071480:APOBEC-3G Deaminase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006239:Haplotypes; D006801:Humans; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human