Amd. Husman et al., Adaptation to promiscuous usage of chemokine receptors is not a prerequisite for human immunodeficiency virus type 1 disease progression, J INFEC DIS, 180(4), 1999, pp. 1106-1115
Fifty percent of individuals infected with human immunodeficiency virus typ
e 1 (HIV-1) progress to AIDS in the presence of only non-syncytium-inducing
(NSI) variants. These rapidly replicating NSI isolates are associated with
a high viral load. The question of whether disease progression in the abse
nce of syncytium-inducing (SI) HIV-1 variants is associated with an expansi
on of the coreceptor repertoire of NSI HIV-1 variants was studied. Biologic
al HIV-1 clones were isolated both early and late in infection from progres
sors and long-term survivors with wild-type or mutant CCR5 or CCR2b genotyp
es and analyzed for their capacity to use CCR1, CCR2b, CCR3, CCR5, and CXCR
4 on U87 cells coexpressing CD4, All HIV- clones were restricted to the use
of CCR5. Absent replication of all HIV-I clones in peripheral blood mononu
clear cells from a CCR5 Delta 32 homozygous blood donor confirmed this resu
lt. These findings indicate that an expanded coreceptor repertoire of HIV-1
is not a prerequisite for a progressive clinical course of HIV-1 infection
.