Enhanced HIV-1 replication by chemokines constitutively expressed in secondary lymphoid tissues.
Persistent infection of human immunodeficiency virus (HIV) takes place in the secondary lymphoid tissues even during clinically latent stages. The CC chemokines secondary lymphoid tissue chemokine (SLC) and EBI1-ligand chemokine (ELC) are constitutively expressed in the secondary lymphoid tissues. They share CCR7 expressed on lymphocytes and mature dendritic cells and play key roles in the trafficking of these types of cells into the secondary lymphoid tissues. Here we report that growth of both X4 and R5 strains of HIV-1 in activated peripheral blood T cells was enhanced by SLC. The enhancing effect of SLC was abrogated by pretreatment of cells with pertussis toxin, indicating the involvement of signaling via a receptor coupled with a Galphai class of G-protein. Furthermore, SLC was found to enhance the promoter activity of HIV-1 LTR. These results suggest that signaling via CCR7 has a strong positive effect on HIV growth. Thus, SLC and ELC may contribute to persistent infection of HIV in the secondary lymphoid tissues by promoting viral replication in activated T cells.
Nagira
M
M
Shionogi Institute for Medical Science, Osaka, 566-0022, Japan.
Sato
A
A
Miki
S
S
Imai
T
T
Yoshie
O
O
D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D054421:Chemokine CCL21; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC / Q000378:metabolism* / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000821:virology; D008221:Lymphoid Tissue; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D037342:Pertussis Toxin; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014779:Virus Replication
C515478:CCL21 protein, human; C515370:CCR7 protein, human; C515187:CXCR3 protein, human; D054421:Chemokine CCL21; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go