Attenuation of a human rotavirus vaccine candidate did not correlate with mutations in the NSP4 protein gene.
The NSP4 protein of a simian rotavirus was reported to induce diarrhea following inoculation of mice. If NSP4 is responsible for rotavirus diarrhea in humans, attenuation of a human rotavirus may be reflected in concomitant mutations in the NSP4 gene. After 33 passages in cultured monkey kidney cells, a virulent human rotavirus (strain 89-12) was found to be attenuated in adults, children, and infants. Nucleotide sequence analysis of the NSP4 protein gene revealed only one base pair change between the virulent (unpassaged) and attenuated 89-12 viruses, which resulted from a substitution of alanine for threonine at amino acid 45 of the encoded NSP4 protein. Because both threonine and alanine have been found at position 45 of NSP4 in symptomatic and asymptomatic human rotaviruses, neither amino acid in this position could be established as a marker of virulence. Therefore, attenuation of rotavirus strain 89-12 appears to be unrelated to mutations in the NSP4 gene.
Ward
R L
RL
Division of Infectious Diseases, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. wardd0@chmcc.org
Mason
B B
BB
Bernstein
D I
DI
Sander
D S
DS
Smith
V E
VE
Zandle
G A
GA
Rappaport
R S
RS
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002648:Child; D012321:DNA-Directed RNA Polymerases; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D012401:Rotavirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D014765:Viral Vaccines / Q000276:immunology*
D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; D012321:DNA-Directed RNA Polymerases