title: The effect of HIV-1 Vif polymorphisms on A3G anti-viral activity in an in vivo mouse model.
abstract: Humans encode seven APOBEC3 proteins (A-H), with A3G, 3F and 3H as the major factors restricting HIV-1 replication. HIV-1, however, encodes Vif, which counteracts A3 proteins by chaperoning them to the proteasome where they are degraded. Vif polymorphisms found in HIV-1s isolated from infected patients have varying anti-A3G potency when assayed in vitro, but there are few studies demonstrating this in in vivo models. Here, we created Friend murine leukemia viruses encoding vif alleles that were previously shown to differentially neutralize A3G in cell culture or that were originally found in primary HIV-1 isolates. Infection of transgenic mice expressing different levels of human A3G showed that these naturally occurring Vif variants differed in their ability to counteract A3G during in vivo infection, although the effects on viral replication were not identical to those seen in cultured cells. We also found that the polymorphic Vifs that attenuated viral replication reverted to wild type only in A3G transgenic mice. Finally, we found that the level of A3G-mediated deamination was inversely correlated with the level of viral replication. This animal model should be useful for studying the functional significance of naturally occurring vif polymorphisms, as well as viral evolution in the presence of A3G.
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Cristhian
authors.initials: C
authors.lastname: Cadena
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Microbiology and Immunology, University of Illinois at Chicago College of Medicine, Chicago, IL, 60612, USA.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Stavrou
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Tomaz
authors.initials: T
authors.lastname: Manzoni
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Shilpa S
authors.initials: SS
authors.lastname: Iyer
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bibollet-Ruche
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Weiyu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Browne
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. srross@uic.edu.|Department of Microbiology and Immunology, University of Illinois at Chicago College of Medicine, Chicago, IL, 60612, USA. srross@uic.edu.
authors.forename: Susan R
authors.identifier: 0000-0002-3094-3769
authors.initials: SR
authors.lastname: Ross
mesh_terms: D000071480:APOBEC-3G Deaminase / Q000235:genetics / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D004195:Disease Models, Animal; D005622:Friend murine leukemia virus / Q000235:genetics / Q000502:physiology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011110:Polymorphism, Genetic; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D054320:vif Gene Products, Human Immunodeficiency Virus; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human
keywords: APOBEC3; Cytidine deaminase; HIV; Murine leukemia virus; Vif