Humoral and cell-mediated immune responses in humans to the NSP4 enterotoxin of rotavirus

• Published in: Journal of medical virology 1999-11, Vol.59 (3), p.369-377
• Main Authors: Johansen, Kari, Hinkula, Jorma, Espinoza, Felix, Levi, Mikael, Zeng, Carl, Rudén, Ulla, Vesikari, Timo, Estes, Mary, Svensson, Lennart
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Viral - blood; B- and T-cell responses; Biological and medical sciences; DNA-Directed RNA Polymerases; enterotoxin; Finland; Fundamental and applied biological sciences. Psychology; human; Human viral diseases; Humans; Immunity, Cellular - immunology; Immunoglobulin A - blood; Immunoglobulin G - blood; Infant; Infectious diseases; Medical sciences; Microbiology; Nicaragua; NSP4; Recombinant Proteins - biosynthesis; Recombinant Proteins - immunology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Rotavirus - chemistry; Rotavirus - immunology; Rotavirus Infections - immunology; Rotavirus Infections - virology; Sweden; T-Lymphocytes - metabolism; toxic peptide; Viral diseases; Viral diseases of the digestive system; Viral Nonstructural Proteins - biosynthesis; Viral Nonstructural Proteins - immunology; Virology
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/(SICI)1096-9071(199911)59:3<369::AID-JMV18>3.0.CO;2-N

Rotavirus nonstructural protein NSP4 has recently been suggested to function as a viral enterotoxin and play a role in the pathophysiological mechanism whereby rotaviruses induce diarrhea. The ability of rotavirus NSP4 to stimulate a humoral immune response was examined in naturally infected children and adults, rotavirus vaccinated children, as well as a cellular immune response in adults. In this study, 10 of 10 naturally infected children and 9 of 10 rotavirus‐vaccinated children showed a weak humoral IgG immune response to recombinant NSP4 (rNSP4) and/or a synthetic peptide corresponding to residues 114–134 of NSP4. Modest serum IgG antibody responses were detected in 20 of 20 adults. A cellular immune response to rNSP4 and/or NSP4114–134 were detected in 8 of 10 adults measured either as a T‐cell proliferative response (7 of 10), an increased production of IL‐2 (6 of 10), or increased production of interferon‐γ (8 of 10). These results indicate that NSP4 induces a humoral immune response in humans and show for the first time that NSP4 stimulates a cellular immune response, possibly including cytolytic T‐cells. J. Med. Virol. 59:369–377, 1999. © 1999 Wiley‐Liss, Inc.