title: Human APOBEC3F incorporation into human immunodeficiency virus type 1 particles.
abstract: APOBEC3 proteins are a family of cytidine deaminases that exhibit broad antiretroviral activity. Among APOBEC3 proteins, APOBEC3G (hA3G) and APOBEC3F (hA3F) exhibit the most potent anti-HIV-1 activities. Although the incorporation of hA3F into virions is a prerequisite for exerting its antiviral function, the detail mechanism underlying remains incompletely understood. In this work, we present data showing that the nucleocapsid (NC) domain of HIV-1 Gag and a linker sequence between the two cytidine deaminase domains within hA3F, i.e., 104-156 amino acids, are required for viral packaging of hA3F. A detailed mapping study reveals that the cluster of basic residues surrounding the N-terminal zinc finger (ZF) and the linker region between the ZFs of HIV-1 NC play an important role in A3F incorporation, in addition, at least one of two ZFs is required. A hA3F fragment is able to compete with both hA3G and hA3F for viral incorporation, suggesting a common mechanism underlying virion encapsidation of hA3G and hA3F. Taken together, these results shed a light on the detail mechanism underlying viral incorporation of hA3F.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China. Electronic address: xiaoyulik@hotmail.com.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Obstetrics and Gynecology, Royal Victoria Hospital, McGill University Health Centre (MUHC) Reproductive Center, Montreal, Quebec, Canada.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Zeyun
authors.initials: Z
authors.lastname: Mi
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kleiman
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China. Electronic address: shancen@imb.pumc.edu.cn.
authors.forename: Shan
authors.initials: S
authors.lastname: Cen
mesh_terms: D043525:Cytosine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000201:enzymology* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D014771:Virion / Q000235:genetics / Q000502:physiology; D019065:Virus Assembly; D016335:Zinc Fingers; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase
keywords: APOBEC3F; APOBEC3G; HIV-1; Incorporation; NC