title: A TRIM5alpha-independent post-entry restriction to HIV-1 infection of macaque cells that is dependent on the path of entry.
abstract: The replication of human immunodeficiency type-1 (HIV-1) is restricted in macaque cells, in part due to host factors that provide intrinsic immunity after entry. Here we show that a rhesus macaque epithelial cell line engineered to express human CD4, sMAGI cells, has at least two post-entry restrictions to HIV-1 replication: one that is dependent on a previously described post-entry restriction factor of macaque cells, TRIM5alpha, and another that is primarily TRIM5alpha-independent. The TRIM5alpha restriction, which was observed with particles that had an HIV-1 core pseudotyped with VSV-G envelope, is saturable and can be completely abrogated by introducing TRIM5alpha-specific siRNA into the cells. A similar TRIM5alpha-dependent restriction was observed when sMAGI cells expressing human CCR5 were infected with an R5-HIV-1. In contrast, even when viruses enter sMAGI cells using CD4 and an endogenous rhesus coreceptor at levels sufficient to saturate TRIM5alpha, they do not productively infect the sMAGI cells. Nor does treatment of sMAGI cells with TRIM5alpha-specific siRNA relieve this post-entry restriction; this was true whether the HIV-1 core was pseudotyped with SIV envelope or an R5-HIV-1 envelope. Together these data suggest that there is an alternate restriction to replication, here called Lv3, that is encountered by viruses that enter via interaction with CD4 and an endogenous rhesus coreceptor. Thus, these findings suggest that post-entry events are dependent upon the mechanism by which HIV-1 enters the cell.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA 98109, USA.
authors.forename: Mario Javier
authors.initials: MJ
authors.lastname: Pineda
authors.forename: Brannon R
authors.initials: BR
authors.lastname: Orton
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
mesh_terms: D000818:Animals; D000090103:Antiviral Restriction Factors; D015704:CD4 Antigens / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D019713:Receptors, CCR5 / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication
chemical_list: D000090103:Antiviral Restriction Factors; D015704:CD4 Antigens; D002352:Carrier Proteins; D019713:Receptors, CCR5; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases