NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection

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.

EV71 3D Protein Binds with NLRP3 and Enhances the Assembly of Inflammasome Complex

“…The best-characterized inflammasomes is the NLRP3 inflammasome, which activates the maturation of IL-1β through promoting the cleavage of pro-Casp-1 to generate active subunits, p20 and p10 [14]. NLRP3 inflammasome regulates innate immunity in responding to several RNA viruses, including influenza A virus (IAV) [33], encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV) [34], measles virus (MV) [35], myxoma virus (MYXV) [36], adenovirus (Ad) [37], West Nile virus (WNV) [38], Rabies virus (RV) [39], Herpes simplex virus 1 (HSV-1) [40], Rift valley fever virus (RVFV) [41], human T-lymphotropic virus 1 (HTLV-1) [42], and EV71 [16]. However, the mechanisms underlying the assembly of NLRP3 inflammasome regulated by viruses have not been reported.…”

Role of inflammasome genetics in susceptibility to HPV infection and cervical cancer development

“…Our previously published data reported a similar association with HIV-1 [Pontillo et al, 2012] and HTLV-1 infections [Kamada et al, 2014], emphasizing that the NLRP3-inflammasome plays a key role in innate immune anti-viral response and possibly in subversion of virus persistence and viral clearance.…”

“…Twelve single‐SNPs in seven inflammasome genes (rs12150220 and rs11651270 in NLRP1 , rs35829419 and rs10754558 in NLRP3 , rs2043211 and rs6509365 in CARD8 , rs1143643 and rs1143629 in IL1B , rs5744256 and rs1834481 in IL18 , rs4758635 in NLRP6 , rs6920220 in TNFAIP3 ) were selected based on previously reported association with viral diseases [Pontillo et al, , ; Motavaf et al, ; Kamada et al, ] or cancer development [Verma et al, ; Palmieri et al, ; Chen et al, ; Ungerbäck et al, ].…”

Inflammasome control of viral infection

“…Surprisingly, this enhanced and prolonged FMLV replication in vivo and resulted in enhanced inflammation. Despite this, NLR containing inflammasome activation may play some protective role during retroviral infection in humans, as polymorphisms in NLRP1 and NLRP3 are more commonly found in patients infected with human T-lymphotropic virus (HTLV-1) or HIV-1 than in uninfected controls [57–59]. …”