Nucleotide Sequence Analysis of Isolates of Human T-Lymphotropic Virus Type 1 of Diverse Geographical Origins

Abstract

Nucleotide sequences for long terminal repeat (LTR), gag, the protease gene, and pol of a human T-lymphotropic virus type 1 (HTLV-1) isolate of probable Caribbean origin (HTLV-1CH) and a Zairian isolate (HTLV-1EL) were determined providing complete proviral sequences for these isolates. These sequences were compared with those available from previously analyzed isolates. Nucleotide sequence differences of 1.2-3.3% were identified among isolates for which complete genetic information was available. Nucleotide sequence diversity was distributed relatively evenly over the genome with 1.3-5.2% differences in the LTR, 1.1-2.9% differences in gag, 0.7-2.1% differences in the protease gene, 0.9-2.5% differences in pol, 0.9-2.4% differences in env, 0.0-1.4% differences in rex, and 0.1-2.6% differences in tax. There were 1.2-2.3% amino acid differences overall, with 0.8-1.6% nonconservative amino acid alterations. Nucleotide differences were not found in regions of the LTR which are important for transcriptional activity or Tax response. Within the Rex-response element, nucleotide differences were found predominantly in loop rather than stem structures, thus, maintaining the overall secondary structure necessary for Rex activity. Evolutionary tree analysis of the sequence differences suggests a predominant clustering of different HTLV1 strains according to geographical origin. An open reading frame was also identified on the minus DNA strand situated between the env and rex/tax genes which exhibits 0.1-6.9% nucleotide sequence variation among HTLV1 strains. The limited sequence variation among HTLV-1 strains is in striking contrast to the extensive heterogeneity seen among human immunodeficiency virus (HIV) strains.

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

“…Furthermore, several HTLV-I proviruses isolated from ATL or HAM/TSP patients as well as HTLV-I-infected asymptomatic carriers have been isolated and sequenced (Yoshida et al, 1982;Josephs et al, 1984;Jacobson et al, 1988;Gessian et al, 1991;Komurian et al, 1991;Nerurkar et al, 1993). Although there was 95% homology between the sequenced clones, a number of the differences in nucleotide sequence between the clones lie in and around the U3 region of the LTR, which contains the viral promoter (Paine et al, 1991;Ratner et al, 1991). Although some evidence has suggested that nucleotide sequence variation within the LTR may not yet correlate in an obvious manner with disease phenotype (Daenke et al, 1990), the precise interactions of cellular factors, the HTLV-Iencoded trans-activator protein Tax, and speci®c LTR sequences that play a role in determining the pathogenic course after infection are not yet fully de®ned and must continue to be examined.…”

Phylogenetic classification of human T cell leukaemia/lymphoma virus type I genotypes in five major molecular and geographical subtypes

“…In these regions, between 0-5 and 20 % of the general population, depending on age and sex, have HTLV-I antibodies and are considered to be healthy HTLV-I carriers. The question whether the same HTLV-I strain could induce several diseases through different pathways, as in the EBV system (De Th6, 1993), or whether there are specific gene mutations that direct tissue tropism and pathogenesis, as in the case of murine leukaemia retroviruses (Desgroseillers et al, 1985;Rassart et al, 1986;Li et al, 1987;Szurek et al, 1988), led to the comparative molecular analysis of different HTLV-I viral strains (Daenke et al, 1990;De et al, 1991;Komurian et al, 1991;Gessain et al, 1991Gessain et al, , 1992aKinoshita et al,Kinoshita et al, 1991 ;Ratner et al, 1991 ;Gessain et al, 1992a). Furthermore, the puzzling epidemiological distribution of HTLV-I with the existence of geographical molecular clusters, and the recent discovery of distant molecular variants of HTLV-I in Central Africa (Ratner et al, 1985;Gessain et al, 1992a, b;Boeri et al, 1993) and Melanesia (Gessain et al, 1991Saksena et al, 1992;Bastian et al, 1993) raised new questions concerning the origin and evolution of this human oncoretrovirus.…”

Molecular epidemiology of human T lymphotropic virus type 1 transmission in Okinawa, Japan.

“…Our finding that most HTLV-1 carriers in Okinawa were infected with the Cosmopolitan strain supports the notion that there is a low rate of genetic drift among the various geographical isolates. 19 Molecular analysis of HTLV-1 strains revealed the geographic distribution. 29 We were unable to confirm the geographical origins of our species because we had sequences covering only 2 generations.…”

“…The portion of the HTLV-1 proviral DNA tested was 1079 bp (gag 279 bp, env 314 bp, and int 486 bp). We also compared the consensus sequences of our HTLV-1 carriers with the ATK-1 3 , MT2, 17,18 CH, 19 HS35, 20 EL, 19 and Mel5 21 sequences. In order to obtain a reference sequence for the gag, env, and int region, a grand consensus was generated by comparing sequences from 18 HTLV-1 carriers.…”