The influence of human genetic variation on Epstein-Barr virus sequence diversity. Scientific Reports
Rüeger, Hammer, and Loetscher et al. looked for associations between the human genome and genetic variants of Epstein-Barr virus (EBV) among individuals living with HIV in the Swiss HIV Cohort Study.
The authors hypothesized that EBV viremia is most prevalent in immunosuppressed individuals, and therefore identified treatment-naïve patients living with HIV with a CD4+ cell count below 200 cells/μL. Human genotyping, as well as EBV genome sequencing, was performed, and joint analyses for associations (so-called genome-to-genome analyses) were done using mixed models.
The study included 206 men and 62 women with a median age of 40 years (range 20-78). Of those, 57.1% of EBV sequences comprised predominantly EBNA T1, 5.7% predominantly EBNA T2, and 37.2% included multiple haplotypes. Genome-wide association studies (GWAS) were performed for 535 EBV amino acids and 52 EBV genes. Significant associations were identified between 25 human SNPs and viral variants mapping to 2 EBV genes and one EBV amino acid: the gene BALF5 which is involved in viral DNA replication, the gene BBRF1 which is involved in viral DNA translocation during packaging, and the amino acid BRLF1:p.Lys316Glu which plays a role in reactivation from latency and regulation of viral transcription. Strong associations were observed between the BALF5 gene and 17 SNPs in the human UNC5D gene, which is involved in the regulation of apoptosis.
To summarise, the present study is the first to identify genomic interactions between the human host and EBV. If confirmed in similar studies in HIV uninfected patients with EBV viremia, these findings may contribute to understanding the pathogenic processes and the very diverse clinical consequences of EBV infection.