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HTLV-1-infected asymptomatic carriers compared to HAM/TSP patients over-express the apoptosis- and cytotoxicity-related molecules

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Abstract

HTLV-1 infection causes a chronic progressive debilitating neuroinflammatory disease which is called, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). One of the host defense mechanisms against viral infection is apoptosis which may control HTLV-1 infection. Therefore, we aimed to investigate this process and its interaction with viral factors in HTLV-1-infected asymptomatic carriers (ACs) compared to HAM/TSP patients. Fas, FasL, TRAIL, perforin, granzyme A, granzyme B, and granulysin gene expression and serum levels of Fas, FasL, TRAIL, and granulysin in the peripheral blood of 21 sex- and age-matched healthy controls (HCs), ACs, and HAM/TSP patients were evaluated. Also, the level of granulysin secretion in the cell culture supernatant was measured. Finally, the correlation of the expression of these molecules with HTLV-1 proviral load (PVL), Tax, and HBZ mRNA expression was analyzed. ACs compared to HAM/TSP patients significantly over-expressed the Fas, FasL, TRAIL, perforin, and granzyme B molecules. Fas, FasL, TRAIL, and granulysin serum levels were not different among studied groups; whereas, the secretion of granulysin was significantly decreased in ACs and HAM/TSP patients compared to HCs. Also, HAM/TSP patients expressed higher levels of HTLV-1 PVL, Tax, and HBZ mRNA. In addition, in ACs, inverse correlations between the Fas, FasL, TRAIL, perforin, granzyme B, and granulysin levels with HBZ mRNA expression were seen. ACs compared to HAM/TSP patients over-expressed the apoptosis- and cytotoxicity-related molecules. It could be concluded that successful control of the HTLV-1 infection and suppression of HAM/TSP development stem from the strong apoptosis and cytotoxic activity in the peripheral blood of ACs.

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Acknowledgements

We thank the healthy controls and HTLV-1-infected individuals for their cooperation. This study was financially supported by Grants no: 910236 and 921985 from Mashhad University of Medical Sciences (MUMS).

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Authors and Affiliations

  1. Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Asadollah Mohammadi

  2. Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Asadollah Mohammadi, Bahare Fazeli, Zohreh Poursina & Houshang Rafatpanah

  3. Research Center of Iranian Blood Transfusion Organization, Mashhad, Khorasan Razavi, Iran

    Farahnaz Tehranian

  4. Community Medicine Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Veda Vakili

  5. Department of Neurology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Reza Boostani

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  1. Asadollah Mohammadi
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  2. Bahare Fazeli
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  3. Zohreh Poursina
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  4. Farahnaz Tehranian
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  7. Houshang Rafatpanah
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Correspondence to Reza Boostani or Houshang Rafatpanah.

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Mohammadi, A., Fazeli, B., Poursina, Z. et al. HTLV-1-infected asymptomatic carriers compared to HAM/TSP patients over-express the apoptosis- and cytotoxicity-related molecules. Med Microbiol Immunol 208, 835–844 (2019). https://doi.org/10.1007/s00430-019-00625-6

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  • DOI: https://doi.org/10.1007/s00430-019-00625-6

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