Analysis Of Htlv-I Proviral Load In 202 Ham/Tsp Patients And 243 Asymptomatic Htlv-I Carriers: High Proviral Load Strongly Predisposes To Ham/Tsp

Nagai, Masahiro; Usuku, Koichiro; Matsumoto, Wataru; Kodama, Daisuke; Takenouchi, Norihiro; Moritoyo, Takashi; Hashiguchi, Seiichi; Ichinose, Mamoru; Bangham, Charles R. M.; Izumo, Shuji; Osame, Mitsuhiro

doi:10.3109/13550289809114225

Cited by 567 publications

(312 citation statements)

References 38 publications

Supporting

Mentioning

259

Contrasting

Unclassified

Order By: Relevance

“…Recent evidence suggests that provirus load is also an important factor in the outcome of human T-lymphotropic virus-I (HTLV-I) infection (7)(8)(9)(10). HTLV-I is a persistent virus, infecting 10-20 million people worldwide.…”

mentioning

confidence: 99%

“…HAM͞TSP is a chronic debilitating inflammatory disease of the central nervous system, characterized by axonal damage and demyelination, most pronounced in the midthoracic spinal cord (11). The HTLV-I proviral load is 10-to 100-fold greater in HAM͞TSP patients than in asymptomatic healthy carriers (HCs) of the virus (9,12), although the ranges overlap. The pathogenesis of this condition is not understood.…”

mentioning

confidence: 99%

See 1 more Smart Citation

HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy

Jeffery

Usuku

Hall

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

390

365

View full text Add to dashboard Cite

The risk of disease associated with persistent virus infections such as HIV-I, hepatitis B and C, and human T-lymphotropic virus-I (HTLV-I) is strongly determined by the virus load. However, it is not known whether a persistent class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response reduces viral load and is therefore beneficial or causes tissue damage and contributes to disease pathogenesis. HTLV-I-associated myelopathy (HAM͞TSP) patients have a high virus load compared with asymptomatic HTLV-I carriers. We hypothesized that HLA alleles control HTLV-I provirus load and thus inf luence susceptibility to HAM͞TSP. Here we show that, after infection with HTLV-I, the class I allele HLA-A*02 halves the odds of HAM͞TSP (P < 0.0001), preventing 28% of potential cases of HAM͞TSP. Furthermore, HLA-A*02 ؉ healthy HTLV-I carriers have a proviral load one-third that (P ‫؍‬ 0.014) of HLA-A*02 ؊ HTLV-I carriers. An association of HLA-DRB1*0101 with disease susceptibility also was identified, which doubled the odds of HAM͞TSP in the absence of the protective effect of HLA-A*02. These data have implications for other persistent virus infections in which virus load is associated with prognosis and imply that an efficient antiviral CTL response can reduce virus load and so prevent disease in persistent virus infections.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy

Jeffery

Usuku

Hall

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

390

365

View full text Add to dashboard Cite

show abstract

“…Previous studies have indicated that HTLV-1 proviral load (PVL) is a major risk factor for HAM/TSP (26,27). Tax-specific CD8 ϩ T cells have been shown to reduce HTLV-1 PVL and to prevent asymptomatic carriers from developing ATL (28).…”

mentioning

confidence: 99%

Cellular Immune Responses against Simian T-Lymphotropic Virus Type 1 Target Tax in Infected Baboons

Castro

Giret

Magnani

et al. 2016

J Virol

View full text Add to dashboard Cite

show abstract

“…While most infected persons remain asymptomatic carriers (ACs), 3-5% develop a T-cell malignancy termed adult T-cell leukemia (ATL), and another 0.25-3% develop a chronic progressive inflammatory neurologic disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) 1) . One of the most important pathogenic factors in HAM/TSP is the increased HTLV-1 provirus load in the peripheral blood and cerebrospinal fluid 2,3) , suggesting that the immune control of the virus is inadequate in affected persons. A higher HTLV-1 provirus load increases the risk of HAM/TSP and ATL 2,4) ; therefore, the precise immune mechanisms controlling HTLV-1-infected cells must be characterized in more detail.…”

Section: Introductionmentioning

confidence: 99%

“…One of the most important pathogenic factors in HAM/TSP is the increased HTLV-1 provirus load in the peripheral blood and cerebrospinal fluid 2,3) , suggesting that the immune control of the virus is inadequate in affected persons. A higher HTLV-1 provirus load increases the risk of HAM/TSP and ATL 2,4) ; therefore, the precise immune mechanisms controlling HTLV-1-infected cells must be characterized in more detail. With regard to the host defense mechanisms involved in HTLV-1 infection, the role of HTLV-1specific CD8 + cytotoxic T lymphocytes (CTLs) has been studied 5) .…”

Section: Introductionmentioning

confidence: 99%

Human T-lymphotropic virus type 1 (HTLV-1) and innate immunity

Sato

Azakami

Ando

et al. 2011

Inflammation and Regeneration

View full text Add to dashboard Cite

Human T-cell lymphotropic virus type 1 (HTLV-1) is a T lymphotropic human retrovirus that causes adult T-cell leukemia/lymphoma (ATL) and is associated with immunological disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A higher viral load in HTLV-1-infected individuals increases the risk of HAM/TSP and ATL; furthermore, it affects the disease severity of HAM/TSP. Therefore, the precise immune mechanisms controlling HTLV-1-infected cells must be further characterized. In this regard, the role of HTLV-1-specific CD8+ cytotoxic T lymphocytes (CTLs) has been studied intensively. However, there are few reports describing the role of innate immunity in controlling the proliferation of HTLV-1-infected cells.Natural killer (NK) and invariant natural killer T (iNKT) cells are the cellular components of innate immunity that regulate the immune response to general viral infection and cancers. Dendritic cells (DCs) play important roles in the activation of these NK and iNKT cells as well as CTLs. In this review, we summarize the characteristics of DCs, NK cells, and iNKT cells in individuals infected with HTLV-1.In the peripheral blood of HAM/TSP and ATL patients, the decreased number and impaired functionality of DCs, NK cells, and iNKT cells have been reported. Even in asymptomatic carriers, the functions of these cell populations are perturbed by HTLV-1 infection, while their frequencies are comparable to those of healthy individuals. These observations suggest that abnormalities of DCs, NK cells, and iNKT cells are implicated in the pathogenesis of HTLV-1-associated diseases via insufficient viral control. Rec.3/30

show abstract

Analysis Of Htlv-I Proviral Load In 202 Ham/Tsp Patients And 243 Asymptomatic Htlv-I Carriers: High Proviral Load Strongly Predisposes To Ham/Tsp

Cited by 567 publications

References 38 publications

HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy

HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy

Cellular Immune Responses against Simian T-Lymphotropic Virus Type 1 Target Tax in Infected Baboons

Human T-lymphotropic virus type 1 (HTLV-1) and innate immunity

Contact Info

Product

Resources

About