T. Messele et al., No difference in in vitro susceptibility to HIV type 1 between high-risk HIV-negative ethiopian commercial sex workers and low-risk control subjects, AIDS RES H, 17(5), 2001, pp. 433-441
Host factors such as increased beta -chemokine production, HIV-1 coreceptor
expression level, and HIV-1 coreceptor polymorphism have been thought to i
nfluence susceptibility to HIV-1 infection. To determine the protective rol
e of these factors in Ethiopians who remained HIV-1 uninfected, despite mul
tiple high-risk sexual exposures, we studied 21 Ethiopian women who had bee
n employed as commercial sex workers (CSWs) for five or more years, The HIV
-1-resistant CSWs were compared with low-risk age-matched female controls w
ho had a comparable CD4(+) cell percentage and mean fluorescence intensity
(MFI). Genetic polymorphism in the CCR5, CCR2b, or SDF-1 genes appeared not
to be associated with resistance in the Ethiopian CSWs, Expression levels
of CCR5 and CXCR4 on naive, memory, and total CD4(+) T cells tended to be h
igher in the resistant CSWs, while the production of beta -chemokines RANTE
S, MIP-1 alpha, and MIP-1 beta by phytohemagglutinin (PHA)-stimulated perip
heral blood mononuclear cells (PBMCs) was lower compared with low-risk HIV-
1 negative controls. In vitro susceptibility of PHA-stimulated PBMCs to pri
mary, CCR5-restricted, Ethiopian HIV-1 isolates was comparable between resi
stant CSWs and low-risk controls. in vitro susceptibility was positively co
rrelated to CD4(+) cell mean fluorescence intensity and negatively correlat
ed to CCR5 expression levels, suggesting that infection of PBMCs was primar
ily dependent on expression levels of CD4 and that CCR5 expression, above a
certain threshold, did not further increase susceptibility, Our results sh
ow that coreceptor polymorphism, coreceptor expression levels, beta -chemok
ine production, and cellular resistance to in vitro HIV-1 infection are not
associated with protection in high-risk HIV-1-negative Ethiopian CSWs.