A LYMPH NODE-DERIVED CYTOPATHIC SIMIAN IMMUNODEFICIENCY VIRUS MNE VARIANT REPLICATES IN NONSTIMULATED PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Lymph nodes (LNs) are sites of active human immunodeficiency virus typ e 1 (HIV-1) and simian immunodeficiency virus (SIV) replication and di sease at both early and late stages of infection. Consequently, varian t viruses that replicate efficiently and subsequently cause immune dys function may be harbored in this tissue. To determine whether LN-assoc iated SIVs have an increased capacity to replicate and induce cytopath ology, a molecular clone of SIV was isolated directly from DNA extract ed from unpassaged LN tissue of a pig-tailed macaque (Macaca nemestrin a) infected with SIVMne. The animal had declining CD4(+) T-lymphocyte counts at the time of the LN biopsy. In human CD4(+) T-cell lines, the LN-derived virus, SIVMne027, replicated with relatively slow kinetics and was minimally cytopathic and non-syncytium inducing compared to o ther SIVMne clones. However, in phytohemagglutinin-stimulated pig-tail ed macaque peripheral blood mononuclear cells (PBMCs), SIVMne027 repli cated efficiently and was highly cytopathic for the CD4(+) T-cell popu lation. Interestingly, unlike other SIVMne clones, SIVMne027 also repl icated to a high level in nonstimulated macaque PBMCs. High-lever repl ication depended on the presence of both the T-cell and monocyte/macro phage populations and could be enhanced by interleukin-2 (IL-2). Final ly, the primary determinant governing the ability of SIVMne027 to repl icate in nonstimulated and IL-2-stimulated PBMCs mapped to gag-pol-vif . Together, these data demonstrate that LNs may harbor non-syncytium-i nducing, cytopathic viruses that replicate efficiently and are highly responsive to the effects of cytokines such as IL-2.