Abstract
Several determining factors are involved in HPV infection outcomes; human leukocyte antigen (HLA) polymorphisms have been described as related factors. This study has ascertained the effect of genetic variation on HLA-DRB1 and DQB1 genes on HPV-16/-18/-31/-33/-45 and -58 clearance and redetection in Colombian women. PCR and qPCR were used for viral identification and the Illumina MiSeq system was used for HLA-typing of cervical samples (n = 276). Survival models were adjusted for identifying alleles/haplotypes related to HPV clearance/redetection; L1/L2 protein-epitope binding to MHC-II molecules was also predicted. Significant associations suggested effects favouring or hampering clearance/redetection events depending on the viral type involved in infection, e.g. just DRB1*12:01:01G favoured HPV-16 (coeff: 4.8) and HPV-45 clearance (coeff: 12.65) whilst HPV-18 (coeff: 2E-15), HPV-31 (coeff: 8E-17) and HPV-58 hindered elimination (coeff: 1E-14). An effect was only observed for some alelles when configured as haplotypes, e.g. DRB1*04:07:01G (having the greatest frequency in the target population) was associated with DQB1*02:01:1G or *03:02:03. Epitope prediction identified 23 clearance-related peptides and 29 were redetection-related; eight might have been related to HPV-16/-18 and -58 persistence and one to HPV-18 elimination. HLA allele/haplotype relationship with the course of HPV infection (clearance/redetection) depended on the infecting HPV type, in line with the specific viral epitopes displayed.
Highlights
Human papilloma virus (HPV) is the most common sexually-transmitted viral infection, having around 291 million infections annually[1,2,3]
This study was aimed at identifying human leukocyte antigen (HLA)-DRB1 and DQB1 alleles related to the clearance and redetection of the 6 HPV types having the greatest distribution in Colombia (HR-HPV-16, -18, -31, -33, -45 and -58) in a cohort of Colombian women using generation sequencing (NGS) for HLA typing and quantitative PCR assay for viral detection
Regarding type-specific detection, HPV-16 had the greatest prevalence, followed by HPV-18; variations regarding specific type distribution were found during follow-up
Summary
Human papilloma virus (HPV) is the most common sexually-transmitted viral infection, having around 291 million infections annually[1,2,3]. This study was aimed at identifying HLA-DRB1 and DQB1 alleles related to the clearance and redetection of the 6 HPV types having the greatest distribution in Colombia (HR-HPV-16, -18, -31, -33, -45 and -58) in a cohort of Colombian women using generation sequencing (NGS) for HLA typing and quantitative PCR assay for viral detection. L1 and L2 protein peptides fitting into alleles were analysed for predicting which of them might have been related to infection events regarding each viral type. Such information is relevant to understanding specific infections’ natural history and the genetic factors modulating them. The results should prove useful in identifying inmunological biomarkers enabling establishing HPV infection suceptibility and its clinical course
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