title: CC-chemokines enhance the replication of T-tropic strains of HIV-1 in CD4(+) T cells: role of signal transduction.
abstract: This study demonstrates that several CC-chemokines, including those that inhibit entry and replication of macrophage-tropic strains of HIV, increase the replication of T cell (T)-tropic strains in CD4(+) T cells. Enhancement of T-tropic HIV replication is observed at early stages of replication, requires signaling through inhibitory guanine nucleotide-binding regulatory (Gi) proteins, and is associated with increased cell surface colocalization of CD4 and the T-tropic HIV coreceptor CXCR4. These findings may further our understanding of the factors that influence the replication and spread of T-tropic strains of HIV in vivo and suggest that the use of cell signaling CC-chemokines as therapeutic agents for the purpose of limiting HIV replication in vivo should be approached with caution.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kinter
authors.forename: A
authors.initials: A
authors.lastname: Catanzaro
authors.forename: J
authors.initials: J
authors.lastname: Monaco
authors.forename: M
authors.initials: M
authors.lastname: Ruiz
authors.forename: J
authors.initials: J
authors.lastname: Justement
authors.forename: S
authors.initials: S
authors.lastname: Moir
authors.forename: J
authors.initials: J
authors.lastname: Arthos
authors.forename: A
authors.initials: A
authors.lastname: Oliva
authors.forename: L
authors.initials: L
authors.lastname: Ehler
authors.forename: S
authors.initials: S
authors.lastname: Mizell
authors.forename: R
authors.initials: R
authors.lastname: Jackson
authors.forename: M
authors.initials: M
authors.lastname: Ostrowski
authors.forename: J
authors.initials: J
authors.lastname: Hoxie
authors.forename: R
authors.initials: R
authors.lastname: Offord
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D015704:CD4 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D018946:Chemokine CCL5 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D019742:Chemokines, CC / Q000494:pharmacology* / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D015658:HIV Infections / Q000821:virology; D018023:HIV Seronegativity; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D019718:Receptors, CXCR4 / Q000502:physiology; D015398:Signal Transduction; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
chemical_list: D019380:Anti-HIV Agents; D015704:CD4 Antigens; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019718:Receptors, CXCR4; C111989:aminooxypentane-RANTES; D019204:GTP-Binding Proteins