title: Non-structural protein NSP2 induces heterotypic antibody responses during primary rotavirus infection and reinfection in children.
abstract: Rotaviruses are the single most important causes of severe acute diarrhoea in children worldwide. Despite success in developing vaccines, there is still a lack of knowledge about many components of the immune response, particularly those to non-structural proteins. This study established radioimmunoprecipitation (RIP) assays using labeled G1P[8], G2P[4], and G4P[6] human rotaviruses to examine the spectrum and duration of rotavirus antibodies in sera collected sequentially for 18-36 months from 27 children after hospitalization for primary rotavirus gastroenteritis. Five children experienced rotavirus re-infections. Primary responses detected to non-structural protein NSP2 declined to baseline after 100-150 days. Responses were heterotypic between NSP2 of G1P[8] and G4P[8] rotaviruses. Re-infections after 465-786 days boosted antibody levels to NSP2of both serotypes, together with the appearance of anti-NSP2 to G2P[4], even though there was no evidence of infection with this serotype. We developed an enzyme-immunoassay to measure sequential levels of anti-NSP2 IgG and IgA, using recombinant (heterotypic) NSP2 derived from SA11 (G3P[2]). Anti-NSP2 IgG and IgA were detected in sera from 23/23 (100%) and 18/24 (75%) of children after primary infection, declined to baseline after 100-150 days, were boosted after rotavirus re-infections, and again declined to baseline 150 days later. Anti-NSP2 IgA was also detected after primary infection, in duodenal juice from 14/16 (87%), and faecal extract from 11/19 (57%) of children. Sequential estimation of anti-NSP2 EIA levels in sera could be a sensitive index of rotavirus infection and re-infection. The potential of anti-NSP2 to limit viral replication after re-infection deserves further study.
authors.affiliation: Enteric Virus Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia. carl.kirkwood@mcri.edu.au
authors.forename: Carl D
authors.initials: CD
authors.lastname: Kirkwood
authors.forename: Karen
authors.initials: K
authors.lastname: Boniface
authors.forename: Simone
authors.initials: S
authors.lastname: Richardson
authors.forename: Zenobia F
authors.initials: ZF
authors.lastname: Taraporewala
authors.forename: John T
authors.initials: JT
authors.lastname: Patton
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Bishop
mesh_terms: D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D000917:Antibody Formation; D002675:Child, Preschool; D003720:Densitometry; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D016601:RNA-Binding Proteins / Q000276:immunology*; D015531:Radioimmunoprecipitation Assay; D012008:Recurrence; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology*; D013997:Time Factors; D017361:Viral Nonstructural Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D016601:RNA-Binding Proteins; D017361:Viral Nonstructural Proteins; C079234:NS35 protein, rotavirus