Persistent in vitro infection by human T-cell leukemia-lymphoma virus (HTLV) of normal human T-lymphocytes from blood relatives of patients with HTLV-associated mature T-cell neoplasms.

Abstract

AbstractHuman T‐cell lymphoma‐leukemia virus (HTLV), a novel type‐C retrovirus, has been identified in tumor cells of patients with mature T‐cell neoplasms. Attempts to transmit the first isolate of HTLV designated HTLV‐I(CR) to secondary cultures of animal cells and several attempts to transmit HTLV to normal human T cells, activated with PHA and grown with T‐cell growth factor (TCGF), obtained from randomly selected normal adult donors were unsuccessful. Peripheral blood leukocytes were obtained from blood relatives of patients with HTLV‐positive T‐cell neoplasms. These normal adult T cells were exposed to HTLV, and in 5 of 10 samples tested from three separate families, persistent infection of cultured T‐lymphocytes by HTLV occurred. HTLV infection was monitored by three methods: an indirect membrane immunofluorescence assay for HTLV p19; an in situ hybridization assay for intracellular viral RNA; and electron microscopic analysis for extracellular viral particles. Two of the five infected T‐cell lines have been continuously positive for HTLV for over 24 months in continuous culture. B‐cell lines from the same individuals could not be infected by HTLV‐I(CR). Despite the release of viral particles from the infected cultures detected by electron microscopy, no extracellular reverse transcriptase was found. HTLV infection stimulated increased long‐term growth of the T cells although all HTLV‐I(CR)‐infected cultured cells always remained dependent on the addition of TCGF for growth. Phenotypic characterization of the infected cells by monoclonal antibodies, HLA typing, cytochemical and cell surface markers showed that all the infected cells were mature T cells and were easily distinguished from the cells used as a source of HTLV for infection. The infected cells were either of a predominantly helper or of a suppressor phenotype showing that both mature T‐cell subsets can be infected. Whether these data indicate that there is a genetic basis for susceptibility of human T cells to HTLV infection or reflect an increased sensitivity of some cells to infection by low titers of HTLV remains to be determined. These results provide further evidence for a predominant T‐cell tropism of HTLV.