title: A post-entry role for CD63 in early HIV-1 replication.
abstract: Macrophages and CD4(+) lymphocytes are the major reservoirs for HIV-1 infection. CD63 is a tetraspanin transmembrane protein, which has been shown to play an essential role during HIV-1 replication in macrophages. In this study, we further confirm the requirement of CD63 in early HIV-1 replication events in both macrophages and a CD4(+) cell line. Further analysis revealed that viral attachment and cell-cell fusion were unaffected by CD63 silencing. However, CD63-depleted macrophages showed a significant decrease in the initiation and completion of HIV-1 reverse transcription, affecting subsequent events of the HIV-1 life cycle. Integration of HIV-1 cDNA as well as the formation of 2-LTR circles was notably reduced. Reporter assays showed that CD63 down regulation reduced production of the early HIV protein Tat. In agreement, CD63 silencing also inhibited production of the late protein p24. These findings suggest that CD63 plays an early post-entry role prior to or at the reverse transcription step.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555-0435, USA.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Li
authors.forename: Natallia
authors.initials: N
authors.lastname: Dziuba
authors.forename: Brian
authors.initials: B
authors.lastname: Friedrich
authors.forename: James L
authors.initials: JL
authors.lastname: Murray
authors.forename: Monique R
authors.initials: MR
authors.lastname: Ferguson
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D048348:Reverse Transcription; D060149:Tetraspanin 30; D016662:Virus Integration; D053586:Virus Internalization; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; C554586:CD63 protein, human; D016655:HIV Core Protein p24; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D054322:tat Gene Products, Human Immunodeficiency Virus