title: Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes.
abstract: OBJECTIVE
  Rotavirus infection in at-risk children correlates with production of serum autoantibodies indicative of type 1 diabetes progression. Oral infection with rhesus monkey rotavirus (RRV) accelerates diabetes onset in mice. This relates to their rotavirus-specific serum antibody titre and local pro-inflammatory cytokine induction without pancreatic infection. Our aim was to further investigate the roles of serum antibodies and viral extra-intestinal spread in diabetes acceleration by rotavirus.
  
  
  METHODS
  Rotavirus-specific serum antibody production was detected by ELISA in diabetes-prone mice given either inactivated or low-dose RRV, in relation to their diabetes development. Serum anti-rotavirus antibody titres and infectious virus in lymph nodes were measured in mice given RRV or porcine rotavirus CRW-8. In lymph node cells, rotavirus antigen presence and immune activation were determined by flow cytometry, in conjunction with cytokine mRNA levels.
  
  
  RESULTS
  Acceleration of diabetes by RRV required virus replication, which correlated with antibody presence. CRW-8 induced similar specific total immunoglobulin and IgA titres to those induced by RRV, but did not accelerate diabetes. RRV alone elicited specific serum IgG antibodies with a T helper (Th)1 bias, spread to regional lymph nodes and activated antigen-presenting cells at these sites. RRV increased Th1-specific cytokine expression in pancreatic lymph nodes. Diabetes onset was more rapid in the RRV-infected mice with the greater Th1 bias.
  
  
  CONCLUSIONS
  Acceleration of murine diabetes by rotavirus is virus strain-specific and associated with virus spread to regional lymph nodes, activation of antigen-presenting cells at these sites and induction of a Th1-dominated antibody and cytokine response.
authors.affiliation: Department of Microbiology and Immunology, Gate 11, Royal Parade, The University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Pane
authors.forename: N L
authors.initials: NL
authors.lastname: Webster
authors.forename: K L
authors.initials: KL
authors.lastname: Graham
authors.forename: G
authors.initials: G
authors.lastname: Holloway
authors.forename: C
authors.initials: C
authors.lastname: Zufferey
authors.forename: B S
authors.initials: BS
authors.lastname: Coulson
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology* / Q000821:virology*; D005260:Female; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D012401:Rotavirus / Q000276:immunology* / Q000472:pathogenicity*; D012400:Rotavirus Infections / Q000276:immunology*