Multiple Epstein-Barr virus infections in healthy individuals

Abstract

We employed a newly developed genotyping technique with direct representational detection of LMP-1 gene sequences to study the molecular epidemiology of Epstein-Barr virus (EBV) infection in healthy individuals. Infections with up to five different EBV genotypes were found in two of nine individuals studied. These results support the hypothesis that multiple EBV infections of healthy individuals are common. The implications for the development of an EBV vaccine are discussed.

FIG. 1.

Defined sequence patterns in the carboxy terminus of the EBV LMP-1 gene are used to identify EBV genotypes. Each EBV genotype present represents an independent EBV infection of the host and has been validated for the multiple EBV infections and intrahost EBV evolutionary events that characterize individuals with human immunodeficiency virus and AIDS (43). Intrahost evolution of a previously infecting EBV genotype is recognizable as such and does not result in a change of genotype identity. (A) Fourteen numbered sequence patterns represent the region downstream of the 11-amino-acid repeat region of LMP-1. (B) Eleven-lettered sequence patterns represent the region upstream of the 11-amino-acid repeat region of LMP-1. All 25 sequence patterns represent EBV LMP-1 sequences identified in at least three different individuals and from at least two different geographic locations. EBV genotypes are named based upon the combination of the downstream and upstream patterns present conjointly in the LMP-1 gene (for example, 2a-F1). Symbols: dot, amino acid identity with pattern B958(a); *, synonymous nucleotide substitution; −, amino acid codon deletion. Amino acids are numbered on the basis of the LMP-1 gene of the lymphoblastoid cell line isolate B958.