title: Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations.
abstract: Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution.
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, Changchun, Jilin Province, China; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. Electronic address: wwei6@jlu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin, China.
authors.forename: Haoran
authors.initials: H
authors.lastname: Guo
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin, China.
authors.forename: Min
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Markham
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, Changchun, Jilin Province, China; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. Electronic address: xyu2@jhu.edu.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics*; D002681:China / Q000453:epidemiology; D024882:Drug Resistance, Viral; D056084:Genetic Fitness; D014644:Genetic Variation; D005843:Geography; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D064547:Myxovirus Resistance Proteins / Q000494:pharmacology*; D011159:Population Surveillance; D011487:Protein Conformation; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D036022:Capsid Proteins; C579068:MX2 protein, human; D064547:Myxovirus Resistance Proteins
keywords: Capsid variants; HIV-1; MxB; Positive selection