CCR5 receptor expression is down-regulated in HIV type 2 infection: implication for viral control and protection.
HIV-2 is known to display an attenuated phenotype in vivo with prolonged time to disease and decreased rate of transmission. Observational studies in Senegal have demonstrated protection from HIV-1 infection, although the putative mechanism for immunoprotection remains undefined. We evaluated HIV-2-seropositive women from a cohort of commercial sex workers in Dakar, Senegal and identified individuals with very low surface CCR5 receptor expression on CD4+ T cells. In vitro up-regulation of the CCR5 receptor was readily achieved. Down-regulation of the CCR5 was not correlated with activation markers (HLA-DR), beta-chemokine levels, or plasma viral loads. A correlation was observed with HIV-2-specific CD8+ T cell activity as measured by intracellular cytokine production. We postulate that down-regulation of the CCR5 receptor in HIV-2 infection contributes to slower disease course and to the protective mechanism against HIV-1 superinfection, mediated in part by HIV-2-specific cellular immune responses.
Shea
A
A
California Department of Health Services, Richmond, 94804, USA.
Sarr
Dieng A
DA
Jones
N
N
Penning
L
L
Eisen
G
G
Gueye-Ndiaye
A
A
Mboup
S
S
Kanki
P
P
Cao
H
H
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D019742:Chemokines, CC / Q000097:blood; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000503:physiopathology* / Q000821:virology*; D015498:HIV-2; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D012675:Senegal; D019562:Viral Load
D019742:Chemokines, CC; D016207:Cytokines; D006684:HLA-DR Antigens; D019713:Receptors, CCR5