title: Epstein-Barr virus latent membrane protein 1 genetic variability in peripheral blood B cells and oropharyngeal fluids.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Renzette
authors.forename: Mohan
authors.initials: M
authors.lastname: Somasundaran
authors.forename: Frank
authors.initials: F
authors.lastname: Brewster
authors.forename: James
authors.initials: J
authors.lastname: Coderre
authors.forename: Eric R
authors.initials: ER
authors.lastname: Weiss
authors.forename: Margaret
authors.initials: M
authors.lastname: McManus
authors.forename: Thomas
authors.initials: T
authors.lastname: Greenough
authors.forename: Barbara
authors.initials: B
authors.lastname: Tabak
authors.forename: Manuel
authors.initials: M
authors.lastname: Garber
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Kowalik
authors.forename: Katherine
authors.initials: K
authors.lastname: Luzuriaga
mesh_terms: D001402:B-Lymphocytes / Q000821:virology*; D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D009960:Oropharynx / Q000821:virology*; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014763:Viral Matrix Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins