title: Long-term passage of Vif-null HIV-1 in CD4+T cells expressing sub-lethal levels of APOBEC proteins fails to develop APOBEC resistance.
abstract: APOBEC3G (A3G) is a cytidine deaminase with potent antiviral activity that is antagonized by Vif. A3G is expressed in a cell type-specific manner and some semi-permissive cells, including A3.01, express A3G but fail to block replication of Vif-null HIV-1. Here we explored the semi-permissive nature of A3.01 cells and found it to be defined exclusively by the levels of A3G. Indeed, minor changes in A3G levels rendered A3.01 cells either fully permissive or non-permissive for Vif-null HIV-1. Our data indicate that A3.01 cells express sub-lethal levels of catalytically active A3G that affects Vif-null HIV-1 at the proviral level but does not completely block virus replication due to purifying selection. Attempts to use the selective pressure exerted by such sub-lethal levels of A3G to select for APOBEC-resistant Vif-null virus capable of replicating in H9 cells failed despite passaging virus for five months, demonstrating that Vif is a critical viral accessory protein.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 4, Room 312, 4 Center Drive, MSC 0460, Bethesda, MD 20892, United States.
authors.forename: Eri
authors.initials: E
authors.lastname: Miyagi
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 4, Room 312, 4 Center Drive, MSC 0460, Bethesda, MD 20892, United States.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kao
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 4, Room 312, 4 Center Drive, MSC 0460, Bethesda, MD 20892, United States.
authors.forename: Miyoshi
authors.initials: M
authors.lastname: Fumitaka
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 4, Room 312, 4 Center Drive, MSC 0460, Bethesda, MD 20892, United States.
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 4, Room 312, 4 Center Drive, MSC 0460, Bethesda, MD 20892, United States.
authors.forename: Ron
authors.initials: R
authors.lastname: Plishka
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 4, Room 312, 4 Center Drive, MSC 0460, Bethesda, MD 20892, United States. Electronic address: kstrebel@nih.gov.
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebel
mesh_terms: D000071480:APOBEC-3G Deaminase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D045744:Cell Line, Tumor; D002675:Child, Preschool; D005260:Female; D057809:HEK293 Cells; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D011533:Proviruses / Q000235:genetics / Q000254:growth & development*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D017423:Sequence Analysis, RNA; D014779:Virus Replication / Q000235:genetics*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D012367:RNA, Viral; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human
keywords: A3.01 cells; APOBEC3G; Antiviral resistance; Cytidine deaminase; Deamination; HIV-1; Hypermutation; Purifying selection; Vif; Viral evolution