HLA class II allele polymorphism in an outbreak of chikungunya fever in Middle Andaman, India

Abstract

A sudden upsurge of fever cases with joint pain was observed in the outpatient department, Community Health Centre, Rangat during JulyAugust 2010 in Rangat Middle Andaman, India. The aetiological agent responsible for the outbreak was identified as chikungunya virus (CHIKV), by using RT-PCR and IgM ELISA. The study investigated the association of polymorphisms in the human leucocyte antigen class II genes with susceptibility or protection against CHIKV. One hundred and one patients with clinical features suggestive of CHIKV infection and 104 healthy subjects were included in the study. DNA was extracted and typed for HLA-DRB1 and DQB1 alleles. Based on the amino acid sequences of HLA-DQB1 retrieved from the IMGT/HLA database, critical amino acid differences in the specific peptide-binding pockets of HLA-DQB1 molecules were investigated. The frequencies of HLA-DRB1 alleles were not significantly different, whereas lower frequency of HLA-DQB1*03:03 was observed in CHIKV patients compared with the control population [P = 0Á001, corrected P = 0Á024; odds ratio (OR) = 0, 95% confidence interval (95% CI) 0Á0-0Á331; Peto's OR = 0Á1317, 95% CI 0Á0428-0Á405). Significantly lower frequency of glutamic acid at position 86 of peptidebinding pocket 1 coding HLA-DQB1 genotypes was observed in CHIKV patients compared with healthy controls (P = 0Á004, OR = 0Á307, 95% CI 0Á125-0Á707). Computational binding predictions of CD4 epitopes of CHIKV by NetMHCII revealed that HLA-DQ molecules are known to bind more CHIKV peptides than HLA-DRB1 molecules. The results suggest that HLA-DQB1 alleles and critical amino acid differences in the peptide-binding pockets of HLA-DQB1 alleles might have role in influencing infection and pathogenesis of CHIKV.

Cytokines and Chemokines in Chikungunya Virus Infection: Protection or Induction of Pathology

“…Moreover, the amount or type of CHIKV infection present in different individuals could play a role in the emergence of different clinical manifestations. Lastly, host immunogenetics could be another factor influencing the differences observed in CHIKV infection [45,46].…”

Human Genetic Host Factors and Its Role in the Pathogenesis of Chikungunya Virus Infection

“…Many chronic diseases and their host's interaction with the disease have been studied to understand their immunogenetics. HLA-DR3 (HLA- DRB1 * 0301, DQB1 * 0201) and DR4 (HLA-DRB1 * 04, DQB1 * 0302) are markers for type 1 diabetes in Caucasian populations, but not among Japanese patients ( 78 ). The DRB1 * 07 allele is associated with protection against Dengue virus infection in the Cuban population, but not in the Sri Lankan population ( 79 , 80 ).…”

Genetic control of alphavirus pathogenesis

“…Human leukocyte antigens (HLA) play a major role in adaptive immune response initiation and have been reported to be associated with disease outcome (reviewed in Dendrou et al 2018). Polymorphisms in genes encoding HLA class II molecules, which present peptides to CD4+ T cells, were examined to determine the effect on susceptibility or protection against CHIKV-induced disease (Chaaithanya et al 2013); HLA-DQ molecules were found to bind more CHIKV peptides than HLA-DRB1 molecules, and HLA-DQB1*03:03 and other HLA-DQB1 genotypes containing glutamic acid at position 86 of peptide-binding pocket 1 were found at a lower frequency in CHIKV patients compared to the control population. Toll-like receptors (TLRs) that recognize viral RNA genomes, including TLR-3, TLR-7, and TLR-8, are key activators of the innate immune response, including pro-inflammatory cytokine induction.…”