Humoral and cell-mediated immune responses in humans to the NSP4 enterotoxin of rotavirus.
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 NSP4(114-134) 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-gamma (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.
Johansen
K
K
Department of Women and Child Health, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Hinkula
J
J
Espinoza
F
F
Levi
M
M
Zeng
C
C
Rudén
U
U
Vesikari
T
T
Estes
M
M
Svensson
L
L
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D012321:DNA-Directed RNA Polymerases; D005387:Finland; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D009527:Nicaragua; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D012401:Rotavirus / Q000737:chemistry* / Q000276:immunology; D012400:Rotavirus Infections / Q000276:immunology* / Q000821:virology; D013548:Sweden; D013601:T-Lymphocytes / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis / Q000276:immunology*
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; D012321:DNA-Directed RNA Polymerases