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Assessment of HTLV-1 proviral load, LAT, BIM, c-FOS and RAD51 gene expression in adult T cell leukemia/lymphoma

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Abstract

Adult T cell leukemia/lymphoma (ATLL) is a life-threatening malignancy of HTLV-1 infected Th lymphocytes. In the present study host–virus interactions were investigated by assessment of HTLV-1 proviral load (PVL) and host gene expression. A cross-sectional study was carried out on 18 ATLL, 10 HAM/TSP patients and 18 HTLV-1 asymptomatic carriers (ACs). DNA and mRNA of the peripheral blood mononuclear cells were extracted for PVL and LAT, BIM, c-FOS and RAD51 gene expression measurement using qRT-PCR. The mean PVL in ATLL patients was 11,430 ± 3770 copies/104 which was statistically higher than ACs, 530 ± 119 copies/104, (p < 0.001). The expression of BIM, and c-FOS in ATLL patients were higher than HTLV-1 ACs; however, there were no statistically significant differences. The expression of RAD51 as an essential player on DNA repair showed around 160 times increase in ATLL group (166 ± 95) compared to ACs (1.04 ± 0.34) which is statistically significant (p < 0.001). Interestingly, there was a positive correlation between RAD51 expression and HTLV-PVL. The expression of LAT as a central adaptor in TCR signaling interestingly was around 36 times higher in ATLL group than ACs (ATLL; 41.33 ± 19.91 vs. ACs; 1.15 ± 0.22, p < 0.001). This finding showed that TCR signaling pathway mainly provides the growth factors for transformed cells. Furthermore, the overexpression of RAD51 which has been induced in HTLV-1 infected cells as a consequence of virus replication is not able to overcome the DNA damage toward cell transformation.

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Abbreviations

ACs:

Asymptomatic carriers

AKT:

Protein kinase B

ATLL:

Adult T-cell leukemia/lymphoma

β2m:

β2 microglobulin

cDNA:

Complementary DNA

CML:

Chronic myeloid leukemia

CREB:

c-AMP response element binding protein

HAM/TSP:

HTLV-1-associated myelopathy/tropical spastic paraparesis

HBZ:

HTLV-1 basic zipper factor of oncogenesis

HR:

Homologous recombination

HTLV-1:

Human T-cell leukemia virus type 1

LAT:

Linker for activation of T cells

LDH:

Lactate dehydrogenase

MUMS:

Mashhad University of Medical Sciences

PBMCs:

Peripheral blood mononuclear cells

PVL:

Proviral load

ROS:

Reactive oxygen species

TCD4+ cells:

CD4 T-lymphocytes

TCR:

T-cell receptor

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Acknowledgements

This study was supported by the Vice-chancellor for Research, Mashhad University of Medical Sciences (Grant number 911304) and was the subject of a student thesis for Ms Samaneh Ramezani. Great thanks to our colleagues in Inflammation and Inflammatory Research division, Ms N. Valizadeh, Dr. B. Fazeli, Ms S. Ahmadi Ghezeldasht, Dr. A. Mosavat and Ms A. Zeyaee Mehr.

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Authors and Affiliations

  1. Immunology Research Center, Inflammation and Inflammatory Diseases Division, Medical School, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, 9177948564, Mashhad, Iran

    Samaneh Ramezani, Abbas Shirdel, Houshang Rafatpanah, Mohammad Mehdi Akbarin, Hanieh Tarokhian, Hossein Rahimi, Alireza Bari, Hamid Reza Jahantigh & Seyed Abdolrahim Rezaee

  2. Hematology and Oncology Department, Ghaem Hospital, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran

    Abbas Shirdel, Hossein Rahimi & Alireza Bari

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  1. Samaneh Ramezani
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  2. Abbas Shirdel
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  3. Houshang Rafatpanah
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  4. Mohammad Mehdi Akbarin
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  5. Hanieh Tarokhian
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  9. Seyed Abdolrahim Rezaee
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Correspondence to Seyed Abdolrahim Rezaee.

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Ramezani, S., Shirdel, A., Rafatpanah, H. et al. Assessment of HTLV-1 proviral load, LAT, BIM, c-FOS and RAD51 gene expression in adult T cell leukemia/lymphoma. Med Microbiol Immunol 206, 327–335 (2017). https://doi.org/10.1007/s00430-017-0506-1

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