Epstein-Barr Virus Latent Membrane Protein 1 Genetic Variability in Peripheral Blood B Cells and Oropharyngeal Fluids
| Autor: | Eric R. Weiss, Frank E. Brewster, James A. Coderre, Barbara Tabak, Timothy F. Kowalik, Mohan Somasundaran, Margaret M. McManus, Katherine Luzuriaga, Nicholas Renzette, Manuel Garber, Thomas C. Greenough |
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| Rok vydání: | 2014 |
| Předmět: |
Epstein-Barr Virus Infections
Herpesvirus 4 Human Time Factors Mononucleosis Sequence analysis Molecular Sequence Data Immunology Oropharynx Biology Microbiology Genome Virus Viral Matrix Proteins Young Adult Virology Genetic variation medicine Cluster Analysis Humans Genetic variability Gene Phylogeny B-Lymphocytes Genetic Variation Sequence Analysis DNA Epstein–Barr virus latent membrane protein 1 medicine.disease Genome Replication and Regulation of Viral Gene Expression Insect Science DNA Viral |
| Zdroj: | Journal of Virology. 88:3744-3755 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.03378-13 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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