HTLV-l is a replication-competent retrovirus which can induce cancer in spite of the fact that its genome (1) carries no viral oncogene and (2) does not, following integration of proviral DNA, ris-activate any nearby cellular oncogene. It contains a regulatory gene, tax (Fig. 35-2), the protein product of which, Tax, acts in trans both to up-regulate transcription of all the viral genes in the integrated HTLV proviral DNA and also to initiate the leukemogenic process (see Chapter 11). A second HTLV regulatory gene, rex, encodes a protein Rex that regulates the splicing of RNA transcripts by promoting the production and transport to the cytoplasm of unspliced viral RNA and the incompletely spliced gag/pol and env mRNAs, so allowing the production of new virions. Rex has a negative effect on its own production and that of Tax, because multiple splicing is required to produce the mRNAs for these two regulatory proteins (Fig. 35-2). This negative regulation of Tax and Rex expression by Rex would then lead to decreased expression of all the viral genes, and might reestablish latency. Thus it has been postulated that Rex may orchestrate a state of latency alternating with periods of virus production
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