The influence of human genetic variation on Epstein-Barr virus sequence diversity

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.

A FLOT1 host regulatory allele is associated with a recently expanded Mtb clade in patients with tuberculosis

“…Associations between host variants and specific pathogen genetic loci are not unique to TB, and have recently been found in many other infectious diseases such as human immunodeficiency virus, hepatitis C virus, Epstein-Barr virus and Streptococcus pneumoniae bacteria( 34 – 37 ). Our study argues that inclusion of the genetic sequences of infectious agents can offer novel biological insights to future genetic studies of infectious diseases.…”

Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis

“…Associations between host variants and speci c pathogen genetic loci are not unique to TB, and have recently been found in many other infectious diseases such as human immunode ciency virus, hepatitis C virus, Epstein-Barr virus and Streptococcus pneumoniae bacteria [35][36][37][38] . Our study argues that inclusion of the genetic sequences of infectious agents can offer novel biological insights to future genetic studies of infectious diseases.…”

The role of Epstein–Barr virus in nasopharyngeal carcinoma

“…Furthermore, the majority of studies on EBV genotyping were limited to certain regions. Moreover, it was reported that EBV sequence variation is associated with host sequence variants, hence, joint analyses of host and viral genome variation would help decipher the pathogenesis of NPC and identify novel diagnostic and therapeutic targets (Rüeger et al, 2021). Studies recruiting larger samples involving individuals with different conditions from different ethnic groups and geographical regions are needed to determine the exact association of EBV strains with the geographical distribution and development of the disease.…”