title: Heat shock protein 70 inhibits HIV-1 Vif-mediated ubiquitination and degradation of APOBEC3G.
abstract: The cytidine deaminase APOBEC3G, which is incorporated into nascent virus particles, possesses potent antiviral activity and restricts Vif-deficient HIV-1 replication at the reverse transcription step through deamination-dependent and -independent effects. HIV-1 Vif counteracts the antiviral activity of APOBEC3G by inducing APOBEC3G polyubiquitination and its subsequent proteasomal degradation. In this study, we show that overexpression of heat shock protein 70 (HSP70) blocked the degradation of APOBEC3G in the ubiquitin-proteasome pathway by HIV-1 Vif, rendering the viral particles non-infectious. In addition, siRNA targeted knock-down of HSP70 expression enhanced the Vif-mediated degradation of APOBEC3G. A co-immunoprecipitation study revealed that overexpression of HSP70 inhibited APOBEC3G binding to HIV-1 Vif. Thus, we provide evidence for a host protein-mediated suppression of HIV-1 replication in an APOBEC3G-dependent manner.
authors.affiliation: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sugiyama
authors.forename: Hironori
authors.initials: H
authors.lastname: Nishitsuji
authors.forename: Ayako
authors.initials: A
authors.lastname: Furukawa
authors.forename: Masato
authors.initials: M
authors.lastname: Katahira
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Habu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaku
mesh_terms: D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D054875:Ubiquitination / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*; D054320:vif Gene Products, Human Immunodeficiency Virus
chemical_list: D018840:HSP70 Heat-Shock Proteins; 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