Tax-independent stimulation of human T-cell leukemia virus type-I expression and differential effects on its infectivity by subtoxic and toxic doses of 3-methylcholanthrene.
Using the human T-cell leukemia virus type I (HTLV-I) infected SLB-I T-cell line, we showed in this study that 5-d treatment with the maximal subtoxic 3-methylcholanthrene (3-MC) dose (0.25 microgram/ml), as well as with a 3-MC dose that inhibits 50% of the cell growth (5 micrograms/ml), profoundly increased the level of viral RNA. Exposure to these 3-MC doses for 5 d before transient transfection of HTLV-I LTR-CAT construct into these cells markedly stimulated CAT activity, indicating that 3-MC exerted its effect by a trans-acting mechanism. A similar stimulation was observed when this construct was transfected into 3-MC treated uninfected Jurkat cells, indicating that this trans-acting effect was independent of the viral tax protein. However, although the subtoxic 3-MC dose increased also the capacity of SLB-I cells to transmit the virus to normal peripheral blood lymphocytes in coculture, the toxic dose strongly reduced this capacity. No inhibition by this toxic dose was observed in the viral protein synthesis or processing nor in the final release of the virus from the cells. However, the virions released under the influence of this 3-MC dose were found to contain mainly the uncleaved gag precursor polypeptide and a low level of reverse transcriptase. Thus, the reduced virus transmission capacity of the host cells can be ascribed to this structural defect, which presumably lowered the viral infectivity.
Revazova
T
T
Department of Microbiology and Immunology, Ben Gurion University of the Negev, Beer Sheva, Israel.
Dombrovsky
A
A
Lochelt
M
M
Flugel
R M
RM
Aboud
M
M
D002273:Carcinogens / Q000494:pharmacology*; D002455:Cell Division; D002460:Cell Line; D004249:DNA Damage; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015686:Gene Products, env / Q000032:analysis / Q000378:metabolism; D015683:Gene Products, gag / Q000032:analysis / Q000378:metabolism; D016356:Gene Products, tax / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D006801:Humans; D008214:Lymphocytes; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D012367:RNA, Viral / Q000096:biosynthesis; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D013601:T-Lymphocytes; D014162:Transfection; D014771:Virion / Q000737:chemistry / Q000201:enzymology; D014775:Virus Activation / Q000187:drug effects
D002273:Carcinogens; D015686:Gene Products, env; D015683:Gene Products, gag; D016356:Gene Products, tax; D012367:RNA, Viral; D008748:Methylcholanthrene; D012194:RNA-Directed DNA Polymerase