title: Tetraspanin CD63 is a regulator of HIV-1 replication.
abstract: Macrophages and CD4(+) T-cells 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 HIV-1 replication events in primary human CD4(+) T-cells, dendritic cells, and a CD4(+) cell line. Most interestingly, we also show the evidences for the co-localization and internalization of CD63 and HIV-1 major receptor CD4 in primary human macrophages and CD4(+) cell line by confocal microscopy and Co-Immunoprecipitation assay. Analysis revealed that CD63-depleted CD4(+) T-cells, dendritic cells, and a cell line showed significant decrease in HIV-1 production. Further analysis showed that CD63 down regulation reduced production of the early HIV protein Tat, and affected HIV protein Gag by CD63-Gag interaction. In agreement, CD63 silencing also inhibited production of the late protein p24. Furthermore, we revealed that CD63 silencing has no effect on HIV-1 replication with extensive viral challenge (MOI > 0.2). These findings suggest that CD63 plays a dual-role both in early and late HIV-1 life cycle with a range of HIV-1 infection (MOI < 0.2).
authors.affiliation: Department of Respiratory and Critical Medicine, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Enqing
authors.initials: E
authors.lastname: Fu
authors.affiliation: Department of Respiratory and Critical Medicine, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Respiratory and Critical Medicine, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Respiratory and Critical Medicine, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Deguang
authors.initials: D
authors.lastname: Mu
authors.affiliation: Department of Respiratory and Critical Medicine, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Medicine, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Faguang
authors.initials: F
authors.lastname: Jin
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
authors.forename: Xuefan
authors.initials: X
authors.lastname: Bai
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D045744:Cell Line, Tumor; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D060149:Tetraspanin 30 / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D060149:Tetraspanin 30
keywords: CD4+ T-cells; CD63; HIV-1; dendritic cells; life cycle; protein-protein-interactions (PPIs); siRNA