title: HIV-1 Adapts To Replicate in Cells Expressing Common Marmoset APOBEC3G and BST2.
abstract: Previous studies have shown that a major block to HIV-1 replication in common marmosets operates at the level of viral entry and that this block can be overcome by adaptation of the virus in tissue-cultured cells. However, our current studies indicate that HIV-1 encounters additional postentry blocks in common marmoset peripheral blood mononuclear cells. Here, we show that the common marmoset APOBEC3G (A3G) and BST2 proteins block HIV-1 in cell cultures. Using a directed-evolution method that takes advantage of the natural ability of HIV-1 to mutate during replication, we have been able to overcome these blocks in tissue-cultured cells. In the adapted viruses, specific changes were observed in gag, vif, env, and nef. The contribution of these changes to virus replication in the presence of the A3G and BST2 restriction factors was studied. We found that certain amino acid changes in Vif and Env that arise during adaptation to marmoset A3G and BST2 allow the virus to replicate in the presence of these restriction factors. The changes in Vif reduce expression levels and encapsidation of marmoset APOBEC3G, while the changes in Env increase viral fitness and discretely favor cell-to-cell transmission of the virus, allowing viral escape from these restriction factors.
  
  
  OBJECTIVE
  HIV-1 can infect only humans and chimpanzees. The main reason for this narrow tropism is the presence in many species of dominant-acting factors, known as restriction factors, that block viral replication in a species-specific way. We have been exploring the blocks to HIV-1 in common marmosets, with the ultimate goal of developing a new animal model of HIV-1 infection in these monkeys. In this study, we observed that common marmoset APOBEC3G and BST2, two known restriction factors, are able to block HIV-1 in cell cultures. We have adapted HIV-1 to replicate in the presence of these restriction factors and have characterized the mechanisms of escape. These studies can help in the development of a novel animal model for in vivo infection of marmosets with HIV-1-like viruses.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Oliva
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Hillel
authors.initials: H
authors.lastname: Haim
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Menéndez-Arias
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA b.pacheco.phd@hotmail.com.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pacheco
mesh_terms: D000220:Adaptation, Biological; D019943:Amino Acid Substitution; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002144:Callithrix; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics; D006801:Humans; D009154:Mutation; D014776:Virus Cultivation; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; D054298:Human Immunodeficiency Virus Proteins; D003564:Cytidine Deaminase