CC-chemokines enhance the replication of T-tropic strains of HIV-1 in CD4(+) T cells: role of signal transduction.
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.
Kinter
A
A
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Catanzaro
A
A
Monaco
J
J
Ruiz
M
M
Justement
J
J
Moir
S
S
Arthos
J
J
Oliva
A
A
Ehler
L
L
Mizell
S
S
Jackson
R
R
Ostrowski
M
M
Hoxie
J
J
Offord
R
R
Fauci
A S
AS
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
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019718:Receptors, CXCR4; C111989:aminooxypentane-RANTES; D019204:GTP-Binding Proteins