Rapid onset and progression of myelopathy following an STI: a case for screening?

Caswell, Rachel J; Nall, Peter; Boothby, Meg; Taylor, Graham P.

doi:10.1136/sextrans-2019-053978

Cited by 11 publications

(8 citation statements)

References 9 publications

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“…In Australia, it was thought that mother-to-child transmission could explain the number of cases, but a 2000–2013 cohort of indigenous children and adults found associations of HTLV-1 infection with increasing age, male sex, and previous STIs ( 12 ). There is even documentation of TSP/HAM developed by a female patient who was infected with HTLV-1 by her seropositive partner through sexual transmission, as other routes were dismissed during diagnosis ( 13 ).…”

Section: Sexual Transmission Of Htlv-1mentioning

confidence: 99%

HTLV-1 Is Also a Sexually Transmitted Infection

Martel

Gotuzzo

2022

Front. Public Health

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HTLV-1 is a retrovirus which causes diverse diseases in 10% of its infected population, significantly worsening their quality of life and mortality rate. Even though it is globally distributed and is endemic in many countries (including Peru), it is still highly neglected. It spreads through vertical, sexual and parenteral transmission. As no effective treatment against this virus exist, prevention is required to contain it. The World Health Organization published a technical report on the matter in 2021, with the collaboration of international HTLV-1 experts. However, neither the impact of sexual transmission (cause of the majority of adult cases and infection in non-endemic areas) nor its prevention were considered. Evidence is presented, which shows the magnitude of sexual transmission, its risk factors and preventive measures; hoping it will encourage health workers to help eradicate this infection.

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Section: Sexual Transmission Of Htlv-1mentioning

confidence: 99%

HTLV-1 Is Also a Sexually Transmitted Infection

Martel

Gotuzzo

2022

Front. Public Health

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“…HTLV-1-infected individuals remain asymptomatic and possibly unaware of their infection status (Hinuma et al, 1981; Gonçalves et al, 2010; Gessain and Cassar, 2012), which is especially concerning since a significant route of transmission occurs from mother to child via breastfeeding (Fujino and Nagata, 2000; Einsiedel et al, 2016). Moreover, it is likely that, due to a lack of universal screening recommendations, more people globally are at risk of infection via sexual contact, blood transfusions and organ transplants (Gallo et al, 2016; de Morais et al, 2017; Caswell et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

HTLV-1 Extracellular Vesicles Promote Cell-to-Cell Contact

et al. 2019

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Human T-cell leukemia virus-1 (HTLV-1) is a neglected and incurable retrovirus estimated to infect 5 to 10 million worldwide. Specific indigenous Australian populations report infection rates of more than 40%, suggesting a potential evolution of the virus with global implications. HTLV-1 causes adult T-cell leukemia/lymphoma (ATLL), and a neurological disease named HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Even though HTLV-1 transmission primarily occurs from cell-to-cell, there is still a gap of knowledge regarding the mechanisms of viral spread and disease progression. We have recently shown that Extracellular Vesicles (EVs) ubiquitously produced by cells may be used by HTLV-1 to transport viral proteins and RNA, and elicit adverse effects on recipient uninfected cells. The viral proteins Tax and HBZ are involved in disease progression and impairment of autophagy in infected cells. Here, we show that activation of HTLV-1 via ionizing radiation (IR) causes a significant increase of intracellular Tax, but not EV-associated Tax. Also, lower density EVs from HTLV-1-infected cells, separated by an Iodixanol density gradient, are positive for gp61+++/Tax+++/HBZ+ proteins (HTLV-1 EVs). We found that HTLV-1 EVs are not infectious when tested in multiple cell lines. However, these EVs promote cell-to-cell contact of uninfected cells, a phenotype which was enhanced with IR, potentially promoting viral spread. We treated humanized NOG mice with HTLV-1 EVs prior to infection and observed an increase in viral RNA synthesis in mice compared to control (EVs from uninfected cells). Proviral DNA levels were also quantified in blood, lung, spleen, liver, and brain post-treatment with HTLV-1 EVs, and we observed a consistent increase in viral DNA levels across all tissues, especially the brain. Finally, we show direct implications of EVs in viral spread and disease progression and suggest a two-step model of infection including the release of EVs from donor cells and recruitment of recipient cells as well as an increase in recipient cell-to-cell contact promoting viral spread.

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“…In central Australia, up to 48% of certain ethnic communities in the socially disadvantaged Indigenous population are HTLV-1-infected (Einsiedel et al, 2016), which currently accounts for global worries (Martin et al, 2018). Since up to 90% of infected patients stay lifelong asymptomatic and blood donors are not screened for HTLV-1 infection in most countries, asymptomatic carriers are mainly unaware of their infection and may pass the infection to other people (Caswell et al, 2019). HTLV-1 is transmitted via cell-containing body fluids such as breast milk, blood products, semen, and via organ transplants (Pique and Jones, 2012; Gross and Thoma-Kress, 2016).…”

Section: Introductionmentioning

confidence: 99%

Collagen IV (COL4A1, COL4A2), a Component of the Viral Biofilm, Is Induced by the HTLV-1 Oncoprotein Tax and Impacts Virus Transmission

et al. 2019

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Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent for Adult T-Cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HTLV-1 infects CD4+ T-cells via cell-to-cell transmission requiring reorganization of the cytoskeleton and expression of the viral transactivator and oncoprotein Tax. Viruses spread at the virological synapse (VS), a virus-induced specialized cell-cell contact, by polarized budding into synaptic clefts, and by cell surface transfer of viral biofilms (VBs). Since little is known about Tax’s role in formation of the VB, we asked which component of the VB is regulated by Tax and important for HTLV-1 transmission. Collagens are not only structural proteins of the extracellular matrix and basal membrane but also represent an important component of the VB. Here, we report that among the collagens known to be present in VBs, COL4 is specifically upregulated in the presence of HTLV-1 infection. Further, we found that transient expression of Tax is sufficient to induce COL4A1 and COL4A2 transcripts in Jurkat and CCRF-CEM T-cells, while robust induction of COL4 protein requires continuous Tax expression as shown in Tax-transformed T-cell lines. Repression of Tax led to a significant reduction of COL4A1/A2 transcripts and COL4 protein. Mechanistically, luciferase-based promoter studies indicate that Tax activates the COL4A2 and, to a less extent, the COL4A1 promoter. Imaging showing partial co-localization of COL4 with the viral Gag protein in VBs at the VS and transfer of COL4 and Gag to target cells suggests a role of COL4 in VB formation. Strikingly, in chronically infected C91-PL cells, knockout of COL4A2 impaired Gag transfer between infected T-cells and acceptor T-cells, while release of virus-like particles was unaffected. Taken together, we identified COL4 (COL4A1, COL4A2) as a component of the VB and a novel cellular target of Tax with COL4A2 appearing to impact virus transmission. Thus, this study is the first to provide a link between Tax’s activity and VB formation by hijacking COL4 protein functions.

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Rapid onset and progression of myelopathy following an STI: a case for screening?

Cited by 11 publications

References 9 publications

HTLV-1 Is Also a Sexually Transmitted Infection

HTLV-1 Is Also a Sexually Transmitted Infection

HTLV-1 Extracellular Vesicles Promote Cell-to-Cell Contact

Collagen IV (COL4A1, COL4A2), a Component of the Viral Biofilm, Is Induced by the HTLV-1 Oncoprotein Tax and Impacts Virus Transmission

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