VARIABLE IMMORTALIZING POTENTIAL AND FREQUENT VIRUS LATENCY IN BLOOD-DERIVED T-CELL CLONES INFECTED WITH HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I

Human T-cell leukemia virus type I (HTLV-I)-infected T cells expanded in vitro by single-cell cloning provide a unique system for investigat ing virus-cell interactions in nonimmortalized T cells. By analysis of clones generated randomly from the blood of virus carriers, we confir m that CD4 T cells are the major reservoir of HTLV-I in vivo and show that most infected cells contain a single integrated provirus. Contrar y to the situation in HTLV-I immortalized cell lines, the HTLV-I provi rus was found to be transcriptionally silent in a high proportion of r andomly generated T-cell clones and could not be reactivated by mitoge nic stimulation, The spontaneous proliferation previously documented i n HTLV-l-infected T-cell clones was not observed in silently infected cells, and therefore correlates directly with the expression of tax an d other viral genes. The only cytokine mRNA found to be significantly elevated in the virus-producing clones was interleukin-6; however, rec eptor-blocking experiments argue against a role for IL-6 in the virus- induced cell proliferation. We observed a striking variation in the ab ility of individual HTLV-I-producing clones to immortalize fresh perip heral blood lymphocytes, This ability did not correlate with the level s of viral mRNA expression, gag p24 production, spontaneous proliferat ion, or tax-transactivation, possibly suggesting a role for host cell factors as determinants of viral infectivity or immortalization. Studi es to elucidate the basis of this phenotypic heterogeneity should enha nce our understanding of viral spread and pathogenesis. (C) 1997 by Th e American Society of Hematology.