Evolution in a chronic RNA virus infection: selection on HTLV-I tax protein differs between healthy carriers and patients with tropical spastic paraparesis.
HTLV-I causes T-cell leukemia and tropical spastic paraparesis (TSP) in a minority of infected people, whereas the majority remain healthy. The virus differs little in sequence between isolates but has been shown to have a quasispecies structure. Using the Nei and Gojobori algorithm, we have shown that the proportion of nonsynonymous to synonymous changes in HTLV-I proviral tax gene sequences from healthy seropositive subjects (Dn/Ds = 0.9 to 1.3) is significantly higher than those from TSP patients (Dn/Ds = 0.3 to 0.6). Here we show that the distinction between healthy seropositives and TSP patients can only be seen with proviral tax sequences, but not with cDNA, the amino-terminal or carboxy-terminal half of tax, or the rex gene. The Dn/Ds ratio of proviral tax sequences was used to analyze two TSP patients with atypical features and to investigate the influence of cytotoxic T cells (CTL) on the viral quasispecies.
Niewiesk
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Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Bangham
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CR
D005075:Biological Evolution; D002353:Carrier State / Q000276:immunology / Q000821:virology*; D002908:Chronic Disease; D018076:DNA, Complementary; D016370:Gene Products, rex / Q000235:genetics; D016356:Gene Products, tax / Q000235:genetics*; D014644:Genetic Variation; D016679:Genome, Viral; D015368:Human T-lymphotropic virus 1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000401:mortality / Q000821:virology*; D012641:Selection, Genetic; D013602:T-Lymphocytes, Cytotoxic; D013997:Time Factors
D018076:DNA, Complementary; D016370:Gene Products, rex; D016356:Gene Products, tax