RAPID-HIGH, SYNCYTIUM-INDUCING ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INDUCE CYTOPATHICITY IN THE HUMAN THYMUS OF THE SCID-HU MOUSE

Clinical deterioration in human immunodeficiency virus type 1 (HIV-1) disease is associated with an increased viral burden in the peripheral blood and a loss of circulating CD4(+) T cells. HIV-1 isolates obtain ed prior to this stage of disease often have a ''slow-low,'' non-syncy tium-inducing (NSI) phenotype, whereas those obtained afterwards are o ften characterized as ''rapid-high'' and syncytium inducing (SI). Pair ed NSI and SI isolates from two different patients were inoculated int o the human thymus implants of SCID-hu mice. The two slow-low, NSI iso lates replicated to minimal levels in the grafts and did not induce th ymocyte depletion. In contrast, the two SI isolates from the same pati ents showed high levels of viral replication and induced a marked degr ee of thymocyte depletion, accompanied by evidence of programmed cell death, These observations reveal a correlation between the replicative and cytopathic patterns of HIV-1 isolates in vitro and in the SCID-hu mouse in vivo and provide direct evidence that the biological phenoty pe of HIV-1 switch mag be a causal and not a derivative correlate of H IV-1 disease progression.