title: Unperturbed posttranscriptional regulatory Rev protein function and HIV-1 replication in astrocytes.
abstract: Astrocytes protect neurons, but also evoke proinflammatory responses to injury and viral infections, including HIV. There is a prevailing notion that HIV-1 Rev protein function in astrocytes is perturbed, leading to restricted viral replication. In earlier studies, our finding of restricted viral entry into astrocytes led us to investigate whether there are any intracellular restrictions, including crippled Rev function, in astrocytes. Despite barely detectable levels of DDX3 (Rev-supporting RNA helicase) and TRBP (anti-PKR) in primary astrocytes compared to astrocytic cells, Rev function was unperturbed in wild-type, but not DDX3-ablated astrocytes. As in permissive cells, after HIV-1 entry bypass in astrocytes, viral-encoded Tat and Rev proteins had robust regulatory activities, leading to efficient viral replication. Productive HIV-1 infection in astrocytes persisted for several weeks. Our findings on HIV-1 entry bypass in astrocytes demonstrated that the intracellular environment is conducive to viral replication and that Tat and Rev functions are unperturbed.
authors.affiliation: Department of Pathology, Microbiology and Immunology, and Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
authors.forename: Ashok
authors.initials: A
authors.lastname: Chauhan
mesh_terms: D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005333:Fetus; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D019169:Jurkat Cells; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D053586:Virus Internalization; D014779:Virus Replication / Q000235:genetics*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D053487:DEAD-box RNA Helicases; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D056918:Nuclear Receptor Coactivators; D034741:RNA, Small Interfering; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097573:Red Fluorescent Protein; C486559:NCOA6 protein, human; C514860:rev protein, Human Immunodeficiency Virus-1; C119332:DDX3X protein, human