Abstract
Epstein–Barr virus (EBV) is one of the most common viruses latently infecting humans. Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. To search for a potential imprint of host genomic variation on the EBV sequence, we jointly analyzed paired viral and human genomic data from 268 HIV-coinfected individuals with CD4 + T cell count < 200/mm3 and elevated EBV viremia. We hypothesized that the reactivated virus circulating in these patients could carry sequence variants acquired during primary EBV infection, thereby providing a snapshot of early adaptation to the pressure exerted on EBV by the individual immune response. We searched for associations between host and pathogen genetic variants, taking into account human and EBV population structure. Our analyses revealed significant associations between human and EBV sequence variation. Three polymorphic regions in the human genome were found to be associated with EBV variation: one at the amino acid level (BRLF1:p.Lys316Glu); and two at the gene level (burden testing of rare variants in BALF5 and BBRF1). Our findings confirm that jointly analyzing host and pathogen genomes can identify sites of genomic interactions, which could help dissect pathogenic mechanisms and suggest new therapeutic avenues.
Highlights
Epstein–Barr virus (EBV) is one of the most common viruses latently infecting humans
peripheral blood mononuclear cell (PBMC) samples from 778 Swiss HIV Cohort Study (SHCS) participants were screened for the presence of cellular EBV DNA using RT-PCR
We applied standard Genome-wide association studies (GWAS) quality control (QC) procedures that yielded information for 4′291′179 single nucleotide polymorphisms (SNPs) (Table 1 and Supplementary Figure S2, which shows the distribution of the minor allele frequency spectrum after QC)
Summary
Epstein–Barr virus (EBV) is one of the most common viruses latently infecting humans. Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. Three polymorphic regions in the human genome were found to be associated with EBV variation: one at the amino acid level While one part of the variation observed in pathogen DNA or RNA sequence is present at the transmission event, Scientific Reports | (2021) 11:4586 Another fraction is acquired during the course of an infection, resulting at least partially from selective pressure exerted by the host response on the infectious agent. A G2G analysis for the quickly evolving human immunodeficiency virus (HIV) identified strong associations of single nucleotide polymorphisms (SNPs) in the HLA class I region with multiple amino acid variants across the viral g enome[15]. Recent genome sequencing efforts demonstrated that the same holds true for Epstein–Barr virus (EBV)[22,23]
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