Pathogenesis

HTLV probably enters the body principally inside infected CD4 lymphocytes in semen or blood, as well as vertically from mother to infant via breast milk

Fig. 35-2 HTLV provirus genome, showing the position of the LTRs, encoded structural genes {gag, pro, pol, em'), and nonstructural genes (hn, rex), which are divided genes as indicated by the dashed lines. The short arrowheads indicate ribosomal frameshift sites. Beneath are shown the RNA transcripts that serve as mRNAs for translation into particular proteins (long arrows); the thinner V-shaped lines represent introns that are removed from the original RNA transcript lo yield the functional spliced mRNA molecules (Courtesy Dr. J. M. Coffin.)

Fig. 35-2 HTLV provirus genome, showing the position of the LTRs, encoded structural genes {gag, pro, pol, em'), and nonstructural genes (hn, rex), which are divided genes as indicated by the dashed lines. The short arrowheads indicate ribosomal frameshift sites. Beneath are shown the RNA transcripts that serve as mRNAs for translation into particular proteins (long arrows); the thinner V-shaped lines represent introns that are removed from the original RNA transcript lo yield the functional spliced mRNA molecules (Courtesy Dr. J. M. Coffin.)

and possibly transplacen tally. It establishes a lifelong persistent infectipn which generally remains subclinical but occasionally induces disease after an incubation period of 10-40 years. The pathogenesis of one of the two major clinical manifestations, T-celJ leukemia/lymphoma, was discussed in detail in Chapter,11. Briefly, the oncogenic potential of HTLV is ascribed to its regulatory gene tux, the product of which transactivates transcription not only from the proviral LTR but also from certain cellular oncogenes as well as from the cellular gene encoding the interleukin-2 (1L-2) receptor, thereby inducing autocrine stimulation of T-cell proliferation and setting in motion a chain of events that may eventually lead to cancer. As will be seen later in this chapter, expression of the HTLV fax gene also induces the production of the pleiotropic cellular DNA-binding transcription factor NF-kB and may thereby serve as" a cofactor in the progression of AIDS by inducing transcription of the integrated HIV provirus.

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