Variation of HLA class I (-A and -C) genes in individuals infected with hepatitis B or hepatitis C virus in Cameroon

Abstract

The Human Leucocyte Antigens (HLA) work in concert with other immune factors to modulate immunity to viral infections. Extensive variation has been reported in the genetic sequences and functions of classical HLA class I genes in many (mostly Western) populations, and several HLA associations with infectious disease outcomes have been reported. Little is known about their role in the susceptibility or resistance to hepatitis viruses in Central African populations. The aim of this study was to determine variants of two HLA class I genes (HLA-A and -C) in adults infected with hepatitis B (HBV)- or -C (HCV) virus in Cameroon. In this case-control study, a total of 169 unrelated adults comprising 68 HCV-infected, 38 HBV-infected and 63 uninfected (controls) individuals participated. Each consented participant was screened for HBV, HCV, and HIV infections and willingly donated a single blood sample for genomic DNA isolation and some clinical laboratory tests. HLA-A and HLA-C were genotyped using previously described sequence-based techniques (SBT). A total of 54 HLA alleles were identified in the study population (27 HLA-A and 27 HLA-C). HLA-A∗23:01 and HLA-C∗07:01 were the most common alleles with genotype frequencies of 31.4% and 29.3%, respectively. Hepatitis individuals were six times more likely to be HLA-A∗30:01 carriers than uninfected controls (OR = 6.30, p = 0.020 (HBV); OR = 6.21, p = 0.010 (HCV), respectively). Similarly, carriers of HLA-C∗17:01 were over-represented in the HBV-infected compared to the uninfected control group (21.9% vs. 6.4%, respectively) suggesting that this allele could play a role in the susceptibility to HBV infection. These findings demonstrate that carriers of HLA-A∗30:01 were over-represented in the hepatitis group compared to uninfected controls while HLA-C∗17:01 was completely absent in the HCV + group.

Increased Prevalence of Unstable HLA-C Variants in HIV-1 Rapid-Progressor Patients

“…HLA-C has been widely studied for its pivotal role in the immune cellular response to viral infections. Previously published studies linked specific HLA-C variants to HPV-related cervical disease [ 27 ] to patients chronically infected by HCV [ 28 ] and by HBV [ 29 ]. The focus of this work was to determine whether there was an association between HLA-C variants’ stability and HIV-1 infection control.…”

Endoplasmic Reticulum Aminopeptidase 1 Is Involved in Anti-viral Immune Response of Hepatitis B Virus by Trimming Hepatitis B Core Antigen to Generate 9-Mers Peptides

“…In addition, HLA-B*35:14 was observed to be a weak binder for both 9-mers at Pos 30 and Pos 29. The previous study has shown that HLA-C*04:01 is one of the most frequent HLA class I alleles in Cameroonian infected with HBV, with a frequency of 37.5% in patients with HBV compared with that of 25.5% in healthy populations ( Yengo et al, 2020 ). In addition, HLA-C*04:01 was also observed to be in association with poor viral control of HIV ( Olvera et al, 2015 ) and severe clinical course of COVID-19 ( Weiner et al, 2021 ).…”

HLA-A*23 Is Associated With Lower Odds of Acute Retroviral Syndrome in Human Immunodeficiency Virus Type 1 Infection: A Multicenter Sub-Saharan African Study

“…Since HLA-A*23 is associated with lower VRC [ 8 ], which is associated with slower disease progression [ 17 ], it is reasonable to hypothesize that HLA-A*23 is associated with slower disease progression, potentially mediated by both lower VRC and ARS. However, elaborate studies are warranted to clearly elucidate associations between HLA-A*23, a common allele in some sub-Saharan African settings [ 18 ], with disease progression, while controlling for confounding factors. Further exploration of the influence and mechanisms of action of HLA-A*23 on the early immune responses and subsequent long-term effects could enable the identification of peptides for priming immune responses in attempts to reduce the inflammatory burden and mitigate disease progression.…”