Pathogenesis of primary R5 human immunodeficiency virus type 1 clones in SCID-hu mice

We studied the replication and cytopathicity in SCID-hu mice of R5 human im munodeficiency virus type 1 (HIV-1) biological clones from early and late s tages of infection of three patients who never developed MT-2 cell syncytiu m-inducing (SI; R5X4 or X4) viruses. Several of the late-stage non-MT-2 cel l syncytium-inducing (NSI; R5) viruses from these patients depleted human C D4(+) thymocytes from SCID-hu mice. Earlier clones from the same patients d id not deplete CD4(+) thymocytes from SCID-hu mice as well as later clones. We studied three R5 HIV-1 clones from patient ACH142 in greater detail. Tw o of these clones were obtained prior to the onset of AIDS; the third was o btained following the AIDS diagnosis. In GHOST cell infection assays, all t hree ACH142 R5 HIV-1 clones could infect GHOST cells expressing CCR5 but no t GHOST cells expressing any of nine other HIV coreceptors tested. Furtherm ore, these patient clones efficiently infected stimulated peripheral blood mononuclear cells from a normal donor but not those from a homozygous CCR5 Delta 32 individual. Statistical analyses of data obtained from infection o f SCID-hu mice with patient ACH142 R5 clones revealed that only the AIDS-as sociated clone significantly depleted CD4(+) thymocytes from SCID-hu mice. This clone also replicated to higher levels in SCID-hu mice than the two ea rlier clones, and a significant correlation between viral replication and C D4(+) thymocyte depletion was observed. Our results indicate that an intrin sic property of AIDS-associated R5 patient clones causes their increased re plication and cytopathic effects in SCID-hu mice and likely contributes to the development of AIDS in patients who harbor only R5 quasispecies of HIV- 1.