title: HIV-1 Exploits the Host Factor RuvB-like 2 to Balance Viral Protein Expression.
abstract: The correct ratio of the HIV-1 structural protein Gag to the envelope protein (Env) is important for maximal virion infectivity. How the virus ensures the production of Gag and Env proteins in an appropriate ratio remains unknown. We report that HIV-1 exploits the host factor RuvB-like 2 (RVB2) to balance relative expression of Gag and Env for efficient production of infectious virions. RVB2 inhibits Gag expression by interacting with both the encoded Matrix (MA) domain of Gag protein and 5' UTR of the translating mRNA and promoting mRNA degradation in a translation-dependent manner. This inhibitory activity of RVB2 is antagonized by Env through competitive interaction with MA, allowing Gag synthesis to proceed when Env levels are adequate for virion assembly. In HIV-1-positive patients, RVB2 levels positively correlate with viral loads and disease progression status. These findings reveal a mechanism by which HIV-1 regulates its protein expression.
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Mu
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, Columbia University Medical Center, Columbia University, New York NY, 10032, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xinlu
authors.initials: X
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Xuan
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, Columbia University Medical Center, Columbia University, New York NY, 10032, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Goff
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: gaogx@moon.ibp.ac.cn.
authors.forename: Guangxia
authors.initials: G
authors.lastname: Gao
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004265:DNA Helicases / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D054299:env Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis*
chemical_list: D002352:Carrier Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human