Abstract
SAMHD1, a host dNTPase, acts as a retroviral restriction factor by degrading the pool of nucleotides available for the initial reverse transcription of retroviruses, including HTLV-1. Polymorphisms in the SAMDH1 gene may alter the enzymatic expression and influence the course of infection by the virus. The present study investigated the effect of polymorphisms on HTLV-1 infection susceptibility and on progression to disease in 108 individuals infected by HTLV-1 (47 symptomatic and 61 asymptomatic) and 100 individuals in a control group. SAMHD1 rs6029941 (G/A) genotyping and HTLV-1 proviral load measurements were performed using real-time PCR and plasma IFN-α was measured by ELISA. Polymorphism frequency was not associated with HTLV-1 infection susceptibility or with the presence of symptoms. The proviral load was significantly higher in symptomatic individuals with the G allele (p = 0.0143), which presented lower levels of IFN-α (p = 0.0383). SAMHD1 polymorphism is associated with increased proviral load and reduced levels of IFN-α in symptomatic patients, and may be a factor that contributes to the appearance of disease symptoms.
Highlights
HTLV-1 is responsible for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL) and is associated with other inflammatory syndromes, such as rheumatoid arthritis, dermatitis, and uveitis, in addition to autoimmune diseases (Quaresma et al, 2015)
The proviral load test was performed only on 47 samples and the plasma measurement of IFN-α in 52 samples from individuals infected with HTLV-1, because not all samples were viable for these tests
The main restriction factors associated with the inhibition of retroviruses include APOBEC3, TRIM5α, Tetherin, and SAMHD1 (Wilkins and Gale, 2010)
Summary
HTLV-1 is responsible for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL) and is associated with other inflammatory syndromes, such as rheumatoid arthritis, dermatitis, and uveitis, in addition to autoimmune diseases (Quaresma et al, 2015). Most infected individuals do not develop symptoms, and parameters for evaluating the clinical outcome of each carrier remain undefined (Bangham et al, 2015). SAMHD1 is a deoxynucleotide triphosphate triphosphohydrolase (dNTPase) that acts as an intrinsic factor of retroviral restriction, degrading the pool of nucleotides available for the initial reverse transcription, limiting the replication of retroviruses, including HTLV-1 (van Montfoort et al, 2014). Blocking this step prevents the synthesis of double-stranded DNA and disrupts the later stages of the viral replication cycle, including nuclear translocation and integration of DNA into the genome of the host cell (Sze et al, 2013b)
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