Estimation of the infectious viral load required for transfusion‐transmitted human T‐lymphotropic virus type 1 infection (<scp>TT</scp>‐<scp>HTLV</scp>‐1) and of the effectiveness of leukocyte reduction in preventing <scp>TT</scp>‐<scp>HTLV</scp>‐1

Sobata, Rieko; Matsumoto, Chieko; Uchida, Shigeharu; Suzuki, Yoshiharu; Satake, Masahiro; Tadokoro, Kenji

doi:10.1111/vox.12263

Cited by 29 publications

(35 citation statements)

References 44 publications

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“…Previous estimates of infectious dose based on clinical observations or animal models (reviewed elsewhere ) lacked the certainty required for blood safety policy decisions. Conversely, the latest infectious dose estimate , which is orders of magnitude lower than previous estimates, is sufficiently reliable for this purpose. Therefore, it is unlikely that the efficacy of leucodepletion used in our modelling (averaging approximately 95%) was an overestimate, particularly given how closely it corresponds to the 93% reduction in the odds of transfusion–transmission from leucodepleted components observed in the UK .…”

Section: Discussionmentioning

confidence: 93%

Reconsideration of blood donation testing strategy for human T‐cell lymphotropic virus in Australia

et al. 2017

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Transfusion-transmission of HTLV is a minimal risk in Australia even without testing. However, any revision of testing strategy must consider not only risk and cost-effectiveness, but also stakeholder, ethical and regulatory perspectives. Considering all relevant criteria, new-donor testing is judged the optimal strategy because it is able to achieve almost the same outcomes as universal testing, at a fraction of the cost.

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Section: Discussionmentioning

confidence: 93%

Reconsideration of blood donation testing strategy for human T‐cell lymphotropic virus in Australia

et al. 2017

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“…In Japan, all donated blood samples are subjected to leukocyte reduction to reduce the leukocyte count to less than 1 × 10 6 cells per unit . Leukocyte reduction is expected to reduce HTLV‐1 transmission risk in the event that HTLV‐1 positive samples are missed by screening tests …”

Section: Discussionmentioning

confidence: 99%

“…Given that approximately 40% of peripheral blood leukocytes in a healthy individual are mononuclear cells, it was estimated that a PVL of 4% in “PBMCs”—a known risk factor for ATL development—corresponds to a PVL of approximately 1.6% in “leukocytes” here. The detection limit for the pX region was estimated to be four copies per 150 000 host leukocytes with a 50% hit‐rate, or 20 copies per 150 000 host leukocytes with a 95% hit‐rate …”

Section: Methodsmentioning

confidence: 99%

Analysis of HTLV‐1 proviral load (PVL) and antibody detected with various kinds of tests in Japanese blood donors to understand the relationship between PVL and antibody level and to gain insights toward better antibody testing

Matsumoto

Sagara²,

Sobata

et al. 2017

Journal of Medical Virology

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Adult T-cell leukemia/lymphoma (ATL) occurs in approximately 5% of individuals infected with human T-cell leukemia virus type 1 (HTLV-1). A high proviral load (PVL; more than four copies per 100 peripheral blood mononuclear cells (PBMCs) or 1.6 copies per 100 blood leukocytes) and being male are risk factors for ATL development. Whether anti-HTLV-1 antibody level is related to such risk is unknown. Here, PVL and antibody levels were examined using real-time PCR and other tests in 600 HTLV-1 positive screened Japanese blood donors to understand the relationship between PVL and antibody level in asymptomatic carriers and to gain insights toward better antibody testing for HTLV-1 infection. The 430 donors in whom proviral DNA was detected were considered as true positives for HTLV-1 infection. Among donors aged 40 years or older, more males than females had a PVL corresponding to more than 1.6% infected leukocytes, and an antibody titer below the median (P = 0.0018). In antibody tests using an HTLV-1 positive cell line or Env antigens there was a large discrepancy in antibody titer among 13 provirus-positive samples, probably suggesting that antibody-based screening tests should incorporate multiple HTLV-1 antigens, such as Gag and Env antigens.

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“…In addition, it is estimated that 10 6 HTLV-1 particles are needed to infect one primary activated lymphocyte in vitro , underlining the low infectivity of the viral particles6. In vivo , contamination through blood transfusion requires the transfer of at least 10 8 PBMCs7, hence the probability of HTLV-1 infection on leukoreduction is virtually null89. Dendritic cells seem to be the only cell type sensitive to infection through free viral particles10, although infection is still poorly efficient in vitro 11.…”

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confidence: 99%

HTLV-1-induced leukotriene B4 secretion by T cells promotes T cell recruitment and virus propagation

et al. 2017

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The human T-lymphotropic virus type 1 (HTLV-1) is efficiently transmitted through cellular contacts. While the molecular mechanisms of viral cell-to-cell propagation have been extensively studied in vitro, those facilitating the encounter between infected and target cells remain unknown. In this study, we demonstrate that HTLV-1-infected CD4 T cells secrete a potent chemoattractant, leukotriene B4 (LTB4). LTB4 secretion is dependent on Tax-induced transactivation of the pla2g4c gene, which encodes the cytosolic phospholipase A2 gamma. Inhibition of LTB4 secretion or LTB4 receptor knockdown on target cells reduces T-cell recruitment, cellular contact formation and virus propagation in vitro. Finally, blocking the synthesis of LTB4 in a humanized mouse model of HTLV-1 infection significantly reduces proviral load. This results from a decrease in the number of infected clones while their expansion is not impaired. This study shows the critical role of LTB4 secretion in HTLV-1 transmission both in vitro and in vivo.

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Estimation of the infectious viral load required for transfusion‐transmitted human T‐lymphotropic virus type 1 infection (TT‐HTLV‐1) and of the effectiveness of leukocyte reduction in preventing TT‐HTLV‐1

Abstract: The residual number of HTLV-1-infected cells after LR is substantially lower than the viral load necessary for TT-HTLV-1. LR therefore appears to be effective in minimizing the incidence of TT-HTLV-1.

Cited by 29 publications

References 44 publications

Reconsideration of blood donation testing strategy for human T‐cell lymphotropic virus in Australia

Reconsideration of blood donation testing strategy for human T‐cell lymphotropic virus in Australia

Analysis of HTLV‐1 proviral load (PVL) and antibody detected with various kinds of tests in Japanese blood donors to understand the relationship between PVL and antibody level and to gain insights toward better antibody testing

HTLV-1-induced leukotriene B4 secretion by T cells promotes T cell recruitment and virus propagation

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