Increased CCR5 and CXCR4 expression in Ethiopians living in Israel: environmental and constitutive factors.
HIV coreceptors play a major role in determining susceptibility and HIV cell tropism. The present work studied whether the high expression of these coreceptors found on lymphocytes and monocytes of Ethiopian immigrants to Israel (ETH) is the result of environmental and/or constitutive genetic factors. The study of 26 ETH shortly after their arrival to Israel (new ETH), 22 ETH in Israel over 7 years (old ETH), and 20 Caucasian Israelis (non-ETH) enabled us to address this issue. The new ETH had elevated levels of activated HLA-DR+CD4+ and CD38+CD8+ cells in comparison with both old ETH and non-ETH groups (P < 0.01), most probably related to chronic helminthic infections. Surface CCR5 expression, i.e., the percentage of CCR5+ cells and the number of CCR5 molecules/cell, was higher (2- to 3- and 8- to 31-fold, respectively) in activated than in nonactivated CD4+ cells, in all groups. However, CCR5 expression, in both activated and nonactivated CD4+ cells, was higher in both ETH groups than in the non-ETH group. CXCR4 expression was higher in nonactivated CD4+ cells in all groups and was also higher in both ETH groups, in both activated and nonactivated CD4+ cells, than in the non-ETH group. These findings suggest that constitutive factors, in addition to immune activation caused by environmental factors, account for the elevated expression of CCR5 and CXCR4 on CD4+ cells of ETH. This increased HIV coreceptor expression may make ETH more susceptible to HIV infection and may account in part for the rapid spread of AIDS in Ethiopia and the rest of Africa as well.
Kalinkovich
A
A
R. Ben-Ari Institute of Clinical Immunology and AIDS Center, Hebrew University Hadassah Medical School, Rehovot, Israel.
Borkow
G
G
Weisman
Z
Z
Tsimanis
A
A
Stein
M
M
Bentwich
Z
Z
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000349:Africa / Q000453:epidemiology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D004198:Disease Susceptibility; D005002:Ethiopia / Q000453:epidemiology / Q000208:ethnology; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000453:epidemiology; D006684:HLA-DR Antigens / Q000032:analysis; D006373:Helminthiasis / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007557:Israel; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009244:NAD+ Nucleosidase / Q000032:analysis; D019713:Receptors, CCR5 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D012641:Selection, Genetic; D013997:Time Factors
D015703:Antigens, CD; D000943:Antigens, Differentiation; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1