Q531L mutation in the capsid protein of hepatitis E virus genotype 1 causes infections in patients with altered immunity and immunosuppressive condition: Mechanism based on wet lab and in-silico findings

Abstract

ObjectivesThe study aimed to observe the effects of Q531L mutation in the E2s domain of HEV ORF2 on the circulation of the virus among the immunocompetent patients, diabetic patients (immunosuppressive), and pregnant women (altered immunity). MethodsThirty two HEV-RNA samples from pregnant and non-pregnant females were subjected to real time (RT)-qPCR, conventional RT-PCR and Sanger sequencing of HEV ORF2 region covering immunodominant E2s domain (459–606 aa). Liver functions tests using serum samples of the patients were performed. In-silico prediction of CD8+ cytotoxic T lymphocytes (CTL) epitope covering the 531st residue of HEV genotype 1 ORF2/E2s was performed. ResultsThree out of 32 samples harbored a nonsynonymous substitution, resulting in HEV genotype 1 ORF2 531Gln>Leu. The patients with HEV 531Gln had significantly higher serum ALT levels than 531Leu (P = 0.001) and in addition, the former had 173-fold higher viral load than the latter (1,360,869.45 ± 5,298,899.45 vs 784 ± 507.73). The HLA-mutant peptide complexes had higher binding affinities than the HLA-wild type complexes, showing Cluspro2.0/PRODIGY docking scores(Kcal/mol)) of −724.6/−9.2 and −854.2/−9.8 versus −680.1/−8.2 and −757.7/−7.5, respectively. One of the three 531Leu patients was a non-pregnant woman with diabetes and the rest 2 were pregnant. ConclusionsThe hosts with immunosuppressive/altered immunity may provide conducive niches for HEV 531Leu.