Differential response to the cytopathic effects of human T-cell lymphotropic virus type III (HTLV-III) superinfection in T4+ (helper) and T8+ (suppressor) T-cell clones transformed by HTLV-I.
We isolated six human T-cell lymphotropic virus type I (HTLV-I)-transformed T-cell clones carrying the phenotypic markers of helper and suppressor T cells. Five of the transformed T-cell clones produced infectious HTLV-I, but one (clone 55) contained a defective provirus and was therefore not competent for viral replication. To test whether there is interference between HTLV-I and the cytopathic virus HTLV-III in infection and/or their biological effects, we superinfected these T-cell clones with HTLV-III. The recipient cells that we used displayed either the OKT4 or the OKT8 membrane antigens (helper or suppressor phenotype, respectively). The superinfection was successful in all cases, regardless of phenotype of the recipient cells and status of viral production. Both HTLV-III and HTLV-I were expressed by the infected cell lines containing complete HTLV-I proviruses, as demonstrated by electron microscopy and immunofluorescence. However, only HTLV-III in the virus mixture obtained from the culture supernatants was transmitted to the human neoplastic T-cell line H9. The nonproducer clone 55 did not express HTLV-I upon superinfection with HTLV-III. HTLV-III exerted its cytopathic effect on all but one of the superinfected T-cell clones 15-20 days after infection. The exception, clone 67, is also the only cell clone that expresses the phenotypic marker of suppressor T lymphocytes (OKT8); the other clones carry the OKT4 antigen, correlated with helper functions. The virus released from the superinfected clone 67 is cytopathic for fresh peripheral and umbilical-cord blood lymphocytes, suggesting that cellular factors, rather than a genetic change in the virus, may be responsible for the lack of cytopathic effect of HTLV-III on the suppressor T-cell clone 67.
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D000956:Antigens, Viral / Q000032:analysis; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000032:analysis; D017977:Deltaretrovirus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D006801:Humans; D008854:Microscopy, Electron; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013601:T-Lymphocytes / Q000382:microbiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000382:microbiology; D013997:Time Factors; D014779:Virus Replication
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D000956:Antigens, Viral; D004279:DNA, Viral; D012194:RNA-Directed DNA Polymerase