Abstract
Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1) infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL)-1 family (IL-1, IL-18 and IL-33) members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls). NLRP3 rs10754558 G/G was associated with protection against HTLV-1 infection (p = 0.012; odds ratio = 0.37). rs10754558 affects NLRP3 mRNA stability; therefore, our results suggest that higher NLRP3 expression may augment first-line defences, leading to the effective protection against HTLV-1 infection.
Highlights
The initial stage of human T-lymphotropic virus 1 (HTLV-1) infection involves cell-cell transmission of HTLV-1 from infected to uninfected T-lymphocytes, followed by the clonal expansion of infected cells, with almost undetectable levels of circulating virions (Pique & Jones 2012)
The pathogenic outcome has been strongly associated with the clonal expansion and infiltration of infected lymphocytes into affected tissues (Lairmore et al 2012), while efficient antigen presentation and cytolytic activity of HTLV-1-specific CD8+ cytotoxic T-lymphocytes have been associated with HTLV-1 proviral load (PVL) control
The inflammasome plays a major role in IL-1ß production and may be involved in the cytoplasmic recognition of HTLV-1; we investigated the possible association between selected single nucleotide polymorphisms (SNPs) in the inflammasome receptor genes NLRP3 and NLRP1 and susceptibility to HTLV-1 infection in HTLV-1-infected patients and controls from northeastern Brazil
Summary
The initial stage of human T-lymphotropic virus 1 (HTLV-1) infection involves cell-cell transmission of HTLV-1 from infected to uninfected T-lymphocytes, followed by the clonal expansion of infected cells, with almost undetectable levels of circulating virions (Pique & Jones 2012). The inflammasome plays a major role in IL-1ß production and may be involved in the cytoplasmic recognition of HTLV-1; we investigated the possible association between selected single nucleotide polymorphisms (SNPs) in the inflammasome receptor genes NLRP3 and NLRP1 and susceptibility to HTLV-1 infection in HTLV-1-infected patients and controls from northeastern Brazil. NLRP1 and NLRP3 single nucleotide polymorphisms (SNPs) frequencies and association results in northeastern Brazilian cohort of human T-lymphotropic virus 1 (HTLV-1) patients and healthy controls (HCs)
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