title: HIV-1 subtype variability in Vif derived from molecular clones affects APOBEC3G-mediated host restriction.
abstract: BACKGROUND
  The host protein APOBEC3G (A3G) can limit HIV-1 replication. Its protective effect is overcome by the HIV-1 'viral infectivity factor' (Vif), which targets A3G for proteosomal degradation. Although Vif is considered to be essential for HIV-1 replication, the effect of Vif variability among commonly used HIV-1 molecular clones of different genetic backgrounds on viral infectiousness and pathogenesis has not been fully determined.
  
  
  METHODS
  We cloned the intact Vif coding regions of available molecular clones of different subtypes into expression vectors. Δvif full-length HIV-1 clonal variants were generated from corresponding subtype-specific full-length molecular clones. Replication-competent viruses were produced in 293T cells in the presence or absence of A3G, with Vif being supplied by the full-length HIV-1 clone or in trans. The extent of A3G-mediated restriction was then determined in a viral replication assay using a reporter cell line.
  
  
  CONCLUSIONS
  In the absence of A3G, Vif subtype origin did not impact viral replication. In the presence of A3G the subtype origin of Vif had a differential effect on viral replication. Vif derived from a subtype C molecular clone was less effective at overcoming A3G-mediated inhibition than Vif derived from either subtype B or CRF02_AG molecular clones.
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, McGill University Health Centre, Montreal, Que., Canada.
authors.forename: Irene
authors.initials: I
authors.lastname: Lisovsky
authors.forename: Susan M
authors.initials: SM
authors.lastname: Schader
authors.forename: Richard D
authors.initials: RD
authors.lastname: Sloan
authors.forename: Maureen
authors.initials: M
authors.lastname: Oliveira
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Coutsinos
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Bernard
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase / Q000276:immunology / Q000378:metabolism*; D014644:Genetic Variation; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D014779:Virus Replication; 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; D003564:Cytidine Deaminase