title: Epstein-Barr virus in oral shedding of children with multiple sclerosis.
abstract: OBJECTIVE
  To investigate Epstein-Barr virus (EBV) oral shedding frequency and EBV genetic diversity in pediatric patients with multiple sclerosis (MS).
  
  
  METHODS
  This was a prospective case-control study. We used PCR-based assays to detect viral DNA in the monthly mouth swabs of 22 pediatric patients with MS and 77 age- and sex-matched healthy controls. EBV-positive samples were further analyzed for sequence variation in the EBV BCRF1 (ebvIL-10) gene using direct DNA sequencing methods, and in the EBV LMP1 gene by mass spectrometry.
  
  
  RESULTS
  Nineteen of the 22 (86.4%) children with MS were seropositive for remote EBV infection compared to 35 out of 77 (45.5%) healthy controls (p = 0.008). Baseline analysis of mouth swabs revealed a higher proportion of EBV-positive samples from EBV-seropositive patients with MS compared to EBV-seropositive healthy controls (52.6% vs 20%, p = 0.007). Longitudinal analysis of monthly swabs revealed average EBV detection rates of 50.6% in patients with MS and 20.4% in controls (p = 0.01). The oral shedding frequencies of Herpesviruses herpes simplex virus-1, cytomegalovirus, human herpesvirus (HHV)-6, and HHV-7 did not differ between groups. Changes in the predominant EBV genetic variants were detected more frequently in patients with MS; however, no specific EBV genetic variant was preferentially associated with MS.
  
  
  CONCLUSIONS
  Children with MS demonstrate abnormally increased rates of EBV viral reactivation and a broader range of genetic variants, suggesting a selective impairment in their immunologic control of EBV.
authors.affiliation: From Neuroscience and Mental Health, Research Institute (C.Y.), The Hospital for Sick Children, Toronto; the Department of Microbiology, Immunology, and Infectious Diseases (R.T.), University of Calgary; the Provincial Public Health Laboratory of Alberta (R.T.), Calgary; the National Microbiology Laboratory (P.C., G.W.), Public Health Agency of Canada, Winnipeg; the Department of Internal Medicine (R.A.M.), University of Manitoba, Winnipeg; the Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Canada; and the Division of Neurology (B.B.), The Children's Hospital of Philadelphia, PA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Yea
authors.forename: Raymond
authors.initials: R
authors.lastname: Tellier
authors.forename: Patrick
authors.initials: P
authors.lastname: Chong
authors.forename: Garrett
authors.initials: G
authors.lastname: Westmacott
authors.forename: Ruth Ann
authors.initials: RA
authors.lastname: Marrie
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.forename: Brenda
authors.initials: B
authors.lastname: Banwell
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D015897:Comorbidity; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000453:epidemiology / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000453:epidemiology / Q000821:virology*; D011446:Prospective Studies; D014763:Viral Matrix Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D017201:Virus Shedding / Q000502:physiology
chemical_list: C066460:BCRF1 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D014764:Viral Proteins