scholarly journals Complete Sequence of a Novel Highly Divergent Simian T-Cell Lymphotropic Virus from Wild-Caught Red-Capped Mangabeys (Cercocebus torquatus) from Cameroon: a New Primate T-Lymphotropic Virus Type 3 Subtype

2002 ◽  
Vol 76 (1) ◽  
pp. 259-268 ◽  
Author(s):  
Laurent Meertens ◽  
Renaud Mahieux ◽  
Philippe Mauclère ◽  
John Lewis ◽  
Antoine Gessain
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Phylogenetic Analyses ◽  
Splice Junction ◽  
Complete Sequence ◽  
Proviral Sequence ◽  
T Lymphotropic Virus ◽  
Cercocebus Torquatus ◽  
Human T Cell ◽  
Type 3

ABSTRACT Among 65 samples obtained from a primate rescue center located in Cameroon, two female adult red-capped mangabeys (Cercocebus torquatus) (CTO-602 and CTO-604), of wild-caught origin, had a peculiar human T-cell lymphotropic virus type 2 (HTLV-2)-like Western blot seroreactivity (p24, RGD21, +/-K55). Analyses of the simian T-cell lymphotropic virus type 3 (STLV-3)/CTO-604 complete proviral sequence (8,919 bp) indicated that this novel strain was highly divergent from HTLV-1 (60% nucleotide similarity), HTLV-2 (62%), or STLV-2 (62%) prototypes. It was, however, related to STLV-3/PH-969 (87%), a divergent STLV strain previously isolated from an Eritrean baboon. The STLV-3/CTO-604 sequence possesses the major open reading frames corresponding to the structural, enzymatic, and regulatory proteins. However, its long terminal repeat is shorter, with only two 21-bp repeats. Furthermore, as demonstrated by reverse transcriptase PCR, this new STLV exhibits significant differences from STLV-3/PH-969 at the mRNA splice junction position level. In all phylogenetic analyses, STLV-3/CTO-604 and STLV-3/PH-969 clustered in a highly supported single clade, indicating an evolutionary lineage independent from primate T-lymphotropic virus type 1 (PTLV-1) and PTLV-2. Nevertheless, the nucleotide divergence between STLV-3/PH-969 and STLV-3/CTO-604 is equivalent to or higher than the divergence observed between the different HTLV-1 or HTLV-2 subtypes. Thus, the STLV-3/CTO-604 strain can be considered the prototype of a second subtype in the PTLV-3 type. The presence of two related viruses in evolutionarily distantly related African monkeys species, living in two opposite ecosystems (rain forest versus desert), reinforces the possible African origin of PTLV and opens new avenues regarding the search for a possible human counterpart of these viruses in individuals exhibiting such HTLV-2-like seroreactivities.

African Origin of Human T-Lymphotropic Virus Type 2 (HTLV-2) Supported by a Potential New HTLV-2d Subtype in Congolese Bambuti Efe Pygmies

1998 ◽  
Vol 72 (5) ◽  
pp. 4327-4340 ◽  
Author(s):  
Anne-Mieke Vandamme ◽  
Marco Salemi ◽  
Marianne Van Brussel ◽  
Hsin-Fu Liu ◽  
Kristel Van Laethem ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Phylogenetic Analyses ◽  
Enzyme Linked Immunosorbent Assay ◽  
African Origin ◽  
Entire Genome ◽  
T Lymphotropic Virus ◽  
Tax Protein ◽  
Human T Cell

ABSTRACT We identified a potential new subtype within human T-cell lymphotropic virus type 2 (HTLV-2), HTLV-2d, present in members of an isolated Efe Bambuti Pygmy tribe. Two of 23 Efe Pygmies were HTLV-2 seropositive, with HTLV-2 Western blot and enzyme-linked immunosorbent assay reactivities. From one of them the entire genome of the HTLV-2 strain Efe2 could be amplified and sequenced. In all gene regions analyzed, this strain was the most divergent HTLV-2 strain, differing by 2.4% (tax/rex) to 10.7% (long terminal repeat) from both subtypes HTLV-2a and HTLV-2b, yet major functional elements are conserved. The similarity between the HTLV-2 Efe2 Gag and Env proteins and the corresponding HTLV-2a and -2b proteins is consistent with the observed serological reactivity. In the proximal pX region, one of the two alternative splice acceptor sites is abolished in HTLV-2 Efe2. Another interesting feature of this potential new subtype is that it has a Tax protein of 344 amino acids (aa), which is intermediate in length between the HTLV-2a Tax protein (331 aa) and the HTLV-2b and -2c Tax proteins (356 aa) and similar to the simian T-cell lymphotropic virus type 2 (STLV-2) PP1664 Tax protein. Together these two findings suggest a different phenotype for the HTLV-2 Efe2 strain. Phylogenetic analyses confirmed that the Pygmy Efe2 strain potentially belonged to a new and quite divergent subtype, HTLV-2d. When the STLV-2 bonobo viruses PP1664 and PanP were used as an outgroup, it was clear that the Pygmy HTLV-2 Efe2 strain had the longest independent evolution and that HTLV-2 evolution is consistent with an African origin.

scholarly journals Human T-Cell Lymphotropic Virus Type 3: Complete Nucleotide Sequence and Characterization of the Human Tax3 Protein

2006 ◽  
Vol 80 (19) ◽  
pp. 9876-9888 ◽  
Author(s):  
Sara Calattini ◽  
Sébastien Alain Chevalier ◽  
Renan Duprez ◽  
Philippe Afonso ◽  
Alain Froment ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Mutational Analysis ◽  
Phylogenetic Analyses ◽  
Amino Acid Level ◽  
Open Reading Frames ◽  
Binding Motif ◽  
Human T Cell ◽  
Type 3

ABSTRACT We and others have recently uncovered the existence of human T-cell lymphotropic virus type 3 (HTLV-3), the third member of the HTLV family. We have now sequenced the full-length HTLV-3Pyl43 provirus. As expected, HTLV-3Pyl43 contains open reading frames corresponding to the gag, pol, env, tax, and rex genes. Interestingly, its long terminal repeat (LTR) includes only two Tax-responsive elements, as is the case for type 3 simian T-cell lymphotropic viruses (STLV-3). Phylogenetic analyses reveal that HTLV-3Pyl43 is closely related to central African STLV-3. Unexpectedly, the proximal pX region of HTLV-3Pyl43 lacks 366 bp compared to its STLV-3 counterpart. Because of this deletion, the previously described RorfII sequence is lacking. At the amino acid level, Tax3Pyl43 displays strong similarities with HTLV-1 Tax, including the sequence of a PDZ class I binding motif. In transient-transfection assays, Tax3Pyl43 activates the transcriptions from HTLV-3, HTLV-1, and HTLV-2 LTRs. Mutational analysis indicates that two functional domains (M22 and M47) important for transactivation through the CREB/ATF or NF-κB pathway are similar but not identical in Tax1 and Tax3Pyl43. We also show that Tax3Pyl43 transactivates the human interleukin-8 and Bcl-XL promoters through the induction of the NF-κB pathway. On the other hand, Tax3Pyl43 represses the transcriptional activity of the p53 tumor suppressor protein as well as the c-Myb promoter. Altogether, these results demonstrate that although HTLV-3 and HTLV-1 have only 60% identity, Tax3Pyl43 is functionally closely related to the transforming protein Tax1 and suggest that HTLV-3, like HTLV-1, might be pathogenic in vivo.

scholarly journals Divergent Simian T-Cell Lymphotropic Virus Type 3 (STLV-3) in Wild-Caught Papio hamadryas papio from Senegal: Widespread Distribution of STLV-3 in Africa

2003 ◽  
Vol 77 (1) ◽  
pp. 782-789 ◽  
Author(s):  
Laurent Meertens ◽  
Antoine Gessain
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Phylogenetic Analyses ◽  
Leukemia Virus ◽  
Papio Hamadryas ◽  
Open Reading Frames ◽  
Interspecies Transmission ◽  
Proviral Sequence ◽  
Cell Leukemia Virus Type ◽  
Human T Cell

ABSTRACT Among eight samples obtained from a French primatology research center, six adult guinea baboons (Papio hamadryas papio), caught in the wild in Senegal, had a peculiar human T-cell leukemia virus type 2 (HTLV-2)-like Western blot seroreactivity (p24+, GD21+, K55+/−). Partial sequence analyses of the tax genes (433 bp) indicated that these baboons were infected by a novel divergent simian T-cell lymphotropic virus (STLV). Analyses of the complete proviral sequence (8,892 bp) for one of these strains (STLV-3/PPA-F3) indicate that this STLV was highly divergent from the HTLV-1 (61.6% of nucleotide similarity), HTLV-2 (61.2%), or STLV-2 (60.6%) prototype. It was, however, much more closely related to the few other known STLV-3 strains, exhibiting 87 and 89% of nucleotide similarity with STLV-3/PHA-PH969 (formerly PTLV-L/PH969) and STLV-3/CTO-604, respectively. The STLV-3/PPA-F3 sequence possesses the major HTLV or STLV open reading frames corresponding to the structural, enzymatic, and regulatory proteins. However, its long terminal repeat comprises only two 21-bp repeats. In all phylogenetic analyses, STLV-3/PPA-F3 clustered together in a highly supported single clade with the other known strains of STLV-3, indicating an independent evolution from primate T-cell lymphotropic virus type 1 (PTLV-1) and PTLV-2. The finding of a new strain of STLV-3 in a West African monkey (Guinea baboon) greatly enlarges the geographical distribution and the host range of species infected by this PTLV type in the African continent. The recent discovery of several different STLV-3 strains in many different African monkey species, often in contact with humans, strongly suggests potential interspecies transmission events, as it was described for STLV-1, between nonhuman primates but also to humans.

scholarly journals Hyperediting of human T-cell leukemia virus type 2 and simian T-cell leukemia virus type 3 by the dsRNA adenosine deaminase ADAR-1

2012 ◽  
Vol 93 (12) ◽  
pp. 2646-2651 ◽  
Author(s):  
Nga Ling Ko ◽  
Emmanuel Birlouez ◽  
Simon Wain-Hobson ◽  
Renaud Mahieux ◽  
Jean-Pierre Vartanian
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Type 3

RNA editing mediated by adenosine deaminases acting on RNA (ADARs) converts adenosine (A) to inosine (I) residues in dsRNA templates. While ADAR-1-mediated editing was essentially described for RNA viruses, the present work addresses the issue for two δ-retroviruses, human T-cell leukemia virus type 2 and simian T-cell leukemia virus type 3 (HTLV-2 and STLV-3). We examined whether ADAR-1 could edit HTLV-2 and STLV-3 virus genomes in cell culture and in vivo. Using a highly sensitive PCR-based method, referred to as 3DI-PCR, we showed that ADAR-1 could hypermutate adenosine residues in HTLV-2. STLV-3 hypermutation was obtained without using 3DI-PCR, suggesting a higher mutation frequency for this virus. Detailed analysis of the dinucleotide editing context showed preferences for 5′ ArA and 5′ UrA. In conclusion, the present observations demonstrate that ADAR-1 massively edits HTLV-2 and STLV-3 retroviruses in vitro, but probably remains a rare phenomenon in vivo.

scholarly journals Selective inhibition of human T-lymphotropic virus type I-transformed human T-cell growth by a tax-targeted conditionally cytotoxic recombinant retrovirus

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2591-2596 ◽  
Author(s):  
M Fujita ◽  
K Murata ◽  
H Shiku
Keyword(s):  
Gene Therapy ◽  
T Cell ◽  
Cell Lines ◽  
Virus Type ◽  
Retroviral Vector ◽  
Leukemic Cells ◽  
Type I ◽  
Retroviral Infection ◽  
T Lymphotropic Virus ◽  
Human T Cell

Abstract Adult T-cell leukemia (ATL), a disorder associated with high mortality rates, arises from human T-lymphotropic virus type I (HTLV-I)-infected CD4+ T cells. We designed a retroviral vector-based gene therapy approach to ATL. The long terminal repeat (LTR) of HTLV-I is transactivated by the viral tax protein. We constructed a hybrid gene consisting of herpes simplex virus thymidine kinase (HSV TK) under the control of the HTLV-I LTR and inserted it into a retroviral vector. When HTLV-I-transformed and tax-expressing human T-cell lines were infected with this recombinant retrovirus (LNLTK alpha virus), they expressed high levels of HSV TK and exhibited increased sensitivity to acyclovir, a nucleoside analog that is converted to the toxic anabolite after phosphorylation by the HSV TK. On the other hand, the retroviral infection had little effect on acyclovir-induced cytotoxicity in HTLV-I- negative human hematopoietic cell lines. Our data may provide the prospect of the gene therapy for ATL by tax-targeted selective elimination of leukemic cells.

Genetic and phylogenetic analyses of human T-cell lymphotropic virus type I variants from Melanesians with an without spastic myelopathy

1994 ◽  
Vol 8 (2-3) ◽  
pp. 155-173 ◽  
Author(s):  
Vivek R. Nerurkar ◽  
Ki-Joon Song ◽  
Rebecca R. Melland ◽  
Richard Yanagihara
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Phylogenetic Analyses ◽  
Type I ◽  
Human T Cell

scholarly journals The Receptor Complex Associated with Human T-Cell Lymphotropic Virus Type 3 (HTLV-3) Env-Mediated Binding and Entry Is Distinct from, but Overlaps with, the Receptor Complexes of HTLV-1 and HTLV-2

2009 ◽  
Vol 83 (10) ◽  
pp. 5244-5255 ◽  
Author(s):  
Kathryn S. Jones ◽  
Ying K. Huang ◽  
Sébastien A. Chevalier ◽  
Philippe V. Afonso ◽  
Cari Petrow-Sadowski ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Surface Glycoprotein ◽  
Binding Studies ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Receptor Complexes ◽  
Human T Cell ◽  
Type 3

ABSTRACT Little is known about the transmission or tropism of the newly discovered human retrovirus, human T-cell lymphotropic virus type 3 (HTLV-3). Here, we examine the entry requirements of HTLV-3 using independently expressed Env proteins. We observed that HTLV-3 surface glycoprotein (SU) binds efficiently to both activated CD4+ and CD8+ T cells. This contrasts with both HTLV-1 SU, which primarily binds to activated CD4+ T cells, and HTLV-2 SU, which primarily binds to activated CD8+ T cells. Binding studies with heparan sulfate proteoglycans (HSPGs) and neuropilin-1 (NRP-1), two molecules important for HTLV-1 entry, revealed that these molecules also enhance HTLV-3 SU binding. However, unlike HTLV-1 SU, HTLV-3 SU can bind efficiently in the absence of both HSPGs and NRP-1. Studies of entry performed with HTLV-3 Env-pseudotyped viruses together with SU binding studies revealed that, for HTLV-1, glucose transporter 1 (GLUT-1) functions at a postbinding step during HTLV-3 Env-mediated entry. Further studies revealed that HTLV-3 SU binds efficiently to naïve CD4+ T cells, which do not bind either HTLV-1 or HTLV-2 SU and do not express detectable levels of HSPGs, NRP-1, and GLUT-1. These results indicate that the complex of receptor molecules used by HTLV-3 to bind to primary T lymphocytes differs from that of both HTLV-1 and HTLV-2.

Prevention of Mother-to-Child Transmission of Human T-Lymphotropic Virus Type-I

PEDIATRICS ◽  
1990 ◽  
Vol 86 (1) ◽  
pp. 11-17
Author(s):  
Yoshiro Tsuji ◽  
Hiroshi Doi ◽  
Tooru Yamabe ◽  
Tadayuki Ishimaru ◽  
Tsutomu Miyamoto ◽  
...  
Keyword(s):  
T Cell ◽  
Breast Milk ◽  
Virus Type ◽  
Type I ◽  
T Lymphotropic Virus ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
Infected Cells ◽  
Mother To Child ◽  
Nagasaki Prefecture

Human T-cell lymphotropic virus type I (HTLV-I), an etiologic human retrovirus of adult T-cell leukemia/lymphoma (ATLL), causes approximately 60 new cases of ATLL each year in Nagasaki Prefecture; essentially all cases are fatal, and they account for approximately 0.5% of total deaths in the area. The estimated life risk for an HTLV-I carrier to develop ATLL is approximately 5%. The major transmission pathway of HTLV-I peculiarly endemic in the Nagasaki Prefecture was studied. The prevalence of HTLV-I infection in children of carrier mothers (21%) was significantly higher than that in children in the general population in the area (1%), and more than 85% of mothers of carrier children were carriers. The breast milk of carrier mothers contained HTLV-I-infected cells and was infectious for marmoset via oral administration. A retrospective survey of children of carrier mothers showed that the prevalence of carrier children of carrier mothers was 17 (39%) of 44 and 0 (0%) of 10 when they were given breast milk only or formula only, respectively. These data provide a powerful basis for devising an intervention measure to block the endemic cycle of HTLV-I; ie, if carrier mothers refrain from breast-feeding, the incidence of ATLL will be significantly reduced some 50 years later.

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