title: A cellular restriction dictates the permissivity of nondividing monocytes/macrophages to lentivirus and gammaretrovirus infection.
abstract: Primate lentiviruses, including HIV-1, transduce terminally differentiated, nondividing myeloid cells; however, these cells are refractory to infection by gammaretroviruses such as murine leukemia virus (MLV). Here, we present evidence that a cellular restriction is the obstacle to transduction of macrophages by MLV. Neutralization of the restriction by Vpx, a primate lentiviral protein previously shown to protect primate lentiviruses from a macrophage restriction, rendered macrophages permissive to MLV infection. We further demonstrate that this restriction prevents transduction of quiescent monocytes by HIV-1. Monocyte-HeLa heterokaryons were resistant to HIV-1 infection, while heterokaryons formed between monocytes and HeLa cells expressing Vpx were permissive to HIV-1 infection. Encapsidation of Vpx within HIV-1 virions conferred the ability to infect quiescent monocytes. Collectively, our results indicate that the relative ability of lentiviruses and gammaretroviruses to transduce nondividing myeloid cells is dependent upon their ability to neutralize a cellular restriction.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Rajnish
authors.initials: R
authors.lastname: Kaushik
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhu
authors.forename: Ruzena
authors.initials: R
authors.lastname: Stranska
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Wu
authors.forename: Mario
authors.initials: M
authors.lastname: Stevenson
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000254:growth & development* / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D014161:Transduction, Genetic; D054334:Viral Regulatory and Accessory Proteins / Q000276:immunology
chemical_list: C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins