UMMS Affiliation

Department of Microbiology and Physiological Systems; Department of Pediatrics; Progam in Molecular Medicine; Department of Bioinformatics and Integrative Biology

Publication Date

4-2014

Document Type

Article

Disciplines

Biochemistry | Bioinformatics | Genetics and Genomics | Molecular Biology | Molecular Genetics | Virology

Abstract

We report the diversity of latent membrane protein 1 (LMP1) gene founder sequences and the level of Epstein-Barr virus (EBV) genome variability over time and across anatomic compartments by using virus genomes amplified directly from oropharyngeal wash specimens and peripheral blood B cells during acute infection and convalescence. The intrahost nucleotide variability of the founder virus was 0.02% across the region sequences, and diversity increased significantly over time in the oropharyngeal compartment (P = 0.004). The LMP1 region showing the greatest level of variability in both compartments, and over time, was concentrated within the functional carboxyl-terminal activating regions 2 and 3 (CTAR2 and CTAR3). Interestingly, a deletion in a proline-rich repeat region (amino acids 274 to 289) of EBV commonly reported in EBV sequenced from cancer specimens was not observed in acute infectious mononucleosis (AIM) patients. Taken together, these data highlight the diversity in circulating EBV genomes and its potential importance in disease pathogenesis and vaccine design.

IMPORTANCE: This study is among the first to leverage an improved high-throughput deep-sequencing methodology to investigate directly from patient samples the degree of diversity in Epstein-Barr virus (EBV) populations and the extent to which viral genome diversity develops over time in the infected host. Significant variability of circulating EBV latent membrane protein 1 (LMP1) gene sequences was observed between cellular and oral wash samples, and this variability increased over time in oral wash samples. The significance of EBV genetic diversity in transmission and disease pathogenesis are discussed.

Keywords

UMCCTS funding

Rights and Permissions

Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.

DOI of Published Version

10.1128/JVI.03378-13

Source

Renzette N, Somasundaran M, Brewster F, Coderre J, Weiss ER, McManus M, Greenough T, Tabak B, Garber M, Kowalik TF, Luzuriaga K. Epstein-barr virus latent membrane protein 1 genetic variability in peripheral blood B cells and oropharyngeal fluids. J Virol. 2014 Apr;88(7):3744-55. doi: 10.1128/JVI.03378-13. Link to article on publisher's site

Journal/Book/Conference Title

Journal of virology

Related Resources

Link to Article in PubMed

PubMed ID

24429365

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