Spastic ataxia associated with human T‐cell lymphotrophic virus type II infection

Harrington, William J.; Sheremata, William A.; Hjelle, Brain; Dube, Dipak K.; Bradshaw, Peggy; Foung, Steven K. H.; Snodgrass, Susan; Toedter, Gary; Cabral, Lisa; Poiesz, Bernard J.

doi:10.1002/ana.410330416

Cited by 103 publications

(34 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10 We have previously reported 4 cases of HAM among HTLV-II patients in the HOST cohort, 4 and there are a number of other HTLV-II HAM case reports in the literature. [28][29][30][31][32][33][34] These results, in addition to the spectrum of milder abnormalities found in our study, support the neuropathologic effects of this virus.…”

Section: Discussionsupporting

confidence: 87%

Neurologic abnormalities in HTLV-I– and HTLV-II–infected individuals without overt myelopathy

Biswas

Engstrom²,

Kaidarova³

et al. 2009

Neurology

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 87%

Neurologic abnormalities in HTLV-I– and HTLV-II–infected individuals without overt myelopathy

Biswas

Engstrom²,

Kaidarova³

et al. 2009

Neurology

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4] In contrast, HTLV-2 is much less pathogenic with only a few cases of variant hairy cell leukemia and neurologic disease associated with infection. [5][6][7][8][9] Both HTLV-1 and HTLV-2 encode the essential Tax protein. Tax acts in trans to activate transcription initiation from the viral promoter.…”

Section: Introductionmentioning

confidence: 99%

PDZ binding motif of HTLV-1 Tax promotes virus-mediated T-cell proliferation in vitro and persistence in vivo

Xie

Yamamoto

Haoudi

et al. 2006

Blood

100

View full text Add to dashboard Cite

HTLV-1 cellular transformation and disease induction is dependent on expression of the viral Tax oncoprotein. PDZ is a modular protein interaction domain used in organizing signaling complexes in eukaryotic cells through recognition of a specific binding motif in partner proteins. Tax-1, but not Tax-2, contains a PDZ-binding domain motif (PBM) that promotes the interaction with several cellular PDZ proteins. Herein, we investigate the contribution of the Tax-1 PBM in HTLV-induced proliferation and immortalization of primary T cells in vitro and viral survival in an infectious rabbit animal model. We generated several HTLV-1 and HTLV-2 Tax viral mutants, including HTLV-1⌬PBM, HTLV-2؉C22(؉PBM), and HTLV-2؉ C18(⌬PBM). All Tax mutants maintained the ability to significantly activate the CREB/ATF or NFB signaling pathways. Microtiter proliferation assays revealed that the Tax-1 PBM significantly increases both HTLV-1-and HTLV-2-induced primary T-cell proliferation. In addition, Tax-1 PBM was responsible for the micronuclei induction activity of Tax IntroductionHTLV-1 and HTLV-2 are highly related complex retroviruses that immortalize and transform T lymphocytes in cell culture and persist in infected individuals. However, the clinical manifestations of infection with these 2 viruses differ. HTLV-1 is associated with adult T-cell leukemia and a variety of immune-mediated disorders, including the chronic neurologic disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis. [1][2][3][4] In contrast, HTLV-2 is much less pathogenic with only a few cases of variant hairy cell leukemia and neurologic disease associated with infection. [5][6][7][8][9] Both HTLV-1 and HTLV-2 encode the essential Tax protein. Tax acts in trans to activate transcription initiation from the viral promoter. 10,11 Tax also modulates the expression or activity of various cellular factors involved in growth and differentiation and disrupts cell-cycle control and DNA repair processes. [12][13][14] Strong evidence suggests that these pleiotropic effects of Tax on cellular processes are required for the transforming or oncogenic capacity of HTLV. 15 Indeed, mutational analysis directly demonstrated that Tax of both HTLV-1 and HTLV-2 is essential for viral-mediated cellular transformation of primary human T cells in culture. [16][17][18] Comparative studies of Tax-1 and Tax-2 revealed that these proteins display many similarities but also some major differences. Tax-1 has a higher intrinsic transactivation activity for the viral promoter than Tax-2. 19 Tax-1, but not Tax-2, is a potent inducer of micronuclei (MN) formation, which is a marker of genetic instability. 20 Tax-2, in contrast to Tax-1, fails to suppress the maturation of CD34 ϩ cells in vitro. 21 Tax-1 has been shown to inhibit p53 function more efficiently than Tax-2. 22,23 Tax-1 morphologically transforms rat fibroblasts with higher efficiency than Tax-2. 24,25 This phenotypic property was attributed to a C-terminal PDZ binding motif (PBM) that is present in Tax-1 but not Ta...

show abstract

“…Endemic HTLV-II infection has also been described in different American Indian tribes, as well as in some indigenous populations of Central Africa [7][8][9][10][11]. No human disease is unequivocally linked to the HTLV-II yet, though the association of HTLV-II with some TSP cases has been reported [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Seroprevalence of Human T-Cell Leukemia/Lymphoma Virus Type I and Type II (HTLV-I/HTLV-II) Infection among Volunteer Blood Donors in Kuwait

et al. 1999

View full text Add to dashboard Cite

Objective: The human T-cell leukemia/lymphoma virus type I (HTLV-I) is an etiologic agent of adult T-cell leukemia/lymphoma and tropical spastic paraparesis. One of the major routes of transmission of the virus is through blood transfusion. The aim of this study was to determine the prevalence of HTLV-I infection in volunteer blood donors in Kuwait. Methods: A donation of 97,602 blood units in Kuwait from March 1995 to October 1997 was tested for antibodies against HTLV-I and related virus (HTLV-II). The testing was carried out in three steps: first screening by enzyme immunoassay (EIA) for anti-HTLV-I/II, second testing of initially positive samples by the EIA and final confirmation of true positives by Western blot. Results: Twenty-one HTLV-I-positive donors have been identified (7 Kuwaitis, 5 Indians, 4 Iranians, 2 Bedouins, 1 Omani, 1 Egyptian and 1 Filipino). None of the EIA-reactive samples was positive for HTLV-II by Western blot. The frequency of HTLV-I-positive blood donations was: 1:4,648 and the infection was significantly more prevalent among Indians and Iranians. Conclusion: The prevalence of HTLV-I infection in blood donors in Kuwait is one of the highest in the world and compulsory screening of blood for HTLV-I is fully justified.

show abstract

Spastic ataxia associated with human T‐cell lymphotrophic virus type II infection

Cited by 103 publications

References 13 publications

Neurologic abnormalities in HTLV-I– and HTLV-II–infected individuals without overt myelopathy

Neurologic abnormalities in HTLV-I– and HTLV-II–infected individuals without overt myelopathy

PDZ binding motif of HTLV-1 Tax promotes virus-mediated T-cell proliferation in vitro and persistence in vivo

Seroprevalence of Human T-Cell Leukemia/Lymphoma Virus Type I and Type II (HTLV-I/HTLV-II) Infection among Volunteer Blood Donors in Kuwait

Contact Info

Product

Resources

About