title: HIV-1 gp120 induces NFAT nuclear translocation in resting CD4+ T-cells.
abstract: The replication of human immunodeficiency virus (HIV) in CD4+ T-cells is strongly dependent upon the state of activation of infected cells. Infection of sub-optimally activated cells is believed to play a critical role in both the transmission of virus and the persistence of CD4+ T-cell reservoirs. There is accumulating evidence that HIV can modulate signal-transduction pathways in a manner that may facilitate replication in such cells. We previously demonstrated that HIV gp120 induces virus replication in resting CD4+ T cells isolated from HIV-infected individuals. Here, we show that in resting CD4+ T-cells, gp120 activates NFATs and induces their translocation into the nucleus. The HIV LTR encodes NFAT recognition sites, and NFATs may play a critical role in promoting viral replication in sub-optimally activated cells. These observations provide insight into a potential mechanism by which HIV is able to establish infection in resting cells, which may have implications for both transmission of HIV and the persistence of viral reservoirs.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1876, USA. ccicala@nih.gov
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicala
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Nina
authors.initials: N
authors.lastname: Censoplano
authors.forename: Catherine
authors.initials: C
authors.lastname: Cruz
authors.forename: Eva
authors.initials: E
authors.lastname: Chung
authors.forename: Elena
authors.initials: E
authors.lastname: Martinelli
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Ven
authors.initials: V
authors.lastname: Natarajan
authors.forename: Donald
authors.initials: D
authors.lastname: VanRyk
authors.forename: Marybeth
authors.initials: M
authors.lastname: Daucher
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D021581:Active Transport, Cell Nucleus; D001665:Binding Sites / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D016325:HIV Long Terminal Repeat / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D050778:NFATC Transcription Factors / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D015699:HIV Envelope Protein gp120; D050778:NFATC Transcription Factors