title: Endocytosis-mediated HIV-1 entry and its significance in the elusive behavior of the virus in astrocytes.
abstract: Astrocytes protect neurons but also evoke a proinflammatory response to injury and viral infections including HIV. We investigated the mechanism of HIV-1 infection in primary astrocytes, which showed minimal but productive viral infection independent of CXCR4. As with ectopic-CD4-expressing astrocytes, lysosomotropic agents led to increased HIV-1 infection in wild-type but not Rabs 5, 7, and 11-ablated astrocytes. Instead, HIV-1 infection was decreased in Rab-depleted astrocytes, corroborating viral entry by endocytosis. HIV-1 produced persistent infection in astrocytes (160 days); no evidence of latent infection was seen. Notably, one caveat is that endosomal modifiers enhanced wild-type HIV-1 infection (M- and T-tropic) in astrocytes, suggesting endocytic entry of the virus. Impeding endocytosis by inhibition of Rab 5, 7 or 11 will inhibit HIV infection in astrocytes. Although the contribution of such low-level infection in astrocytes to neurological complications is unclear, it may serve as an elusive viral reservoir in the central nervous system.
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA; Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29209, USA. Electronic address: Ashok.Chauhan@uscmed.sc.edu.
authors.forename: Ashok
authors.initials: A
authors.lastname: Chauhan
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Mehla
authors.affiliation: Nephrology Laboratory, Christian Medical College, Vellore, Tamil Nadu 632004, India.
authors.forename: Theophilus Sunder
authors.initials: TS
authors.lastname: Vijayakumar
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA.
authors.forename: Indhira
authors.initials: I
authors.lastname: Handy
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology* / Q000821:virology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004705:Endocytosis; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism; D008254:Macaca nemestrina; D056189:Viral Tropism; D014766:Viremia / Q000821:virology; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D054298:Human Immunodeficiency Virus Proteins
keywords: HIV-1 persistence; HIV-LTR; LSP1; Lysosomotropic agents; Proteasome-inhibitors; Rab; TNPO3