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. 1997 Aug;71(8):6267–6270. doi: 10.1128/jvi.71.8.6267-6270.1997

Attenuation of a human rotavirus vaccine candidate did not correlate with mutations in the NSP4 protein gene.

R L Ward 1, B B Mason 1, D I Bernstein 1, D S Sander 1, V E Smith 1, G A Zandle 1, R S Rappaport 1
PMCID: PMC191897  PMID: 9223531

Abstract

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.

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Selected References

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  1. Ball J. M., Tian P., Zeng C. Q., Morris A. P., Estes M. K. Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein. Science. 1996 Apr 5;272(5258):101–104. doi: 10.1126/science.272.5258.101. [DOI] [PubMed] [Google Scholar]
  2. Bernstein D. I., Sander D. S., Smith V. E., Schiff G. M., Ward R. L. Protection from rotavirus reinfection: 2-year prospective study. J Infect Dis. 1991 Aug;164(2):277–283. doi: 10.1093/infdis/164.2.277. [DOI] [PubMed] [Google Scholar]
  3. Bernstein D. I., Smith V. E., Sander D. S., Pax K. A., Schiff G. M., Ward R. L. Evaluation of WC3 rotavirus vaccine and correlates of protection in healthy infants. J Infect Dis. 1990 Nov;162(5):1055–1062. doi: 10.1093/infdis/162.5.1055. [DOI] [PubMed] [Google Scholar]
  4. Both G. W., Siegman L. J., Bellamy A. R., Atkinson P. H. Coding assignment and nucleotide sequence of simian rotavirus SA11 gene segment 10: location of glycosylation sites suggests that the signal peptide is not cleaved. J Virol. 1983 Nov;48(2):335–339. doi: 10.1128/jvi.48.2.335-339.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Broome R. L., Vo P. T., Ward R. L., Clark H. F., Greenberg H. B. Murine rotavirus genes encoding outer capsid proteins VP4 and VP7 are not major determinants of host range restriction and virulence. J Virol. 1993 May;67(5):2448–2455. doi: 10.1128/jvi.67.5.2448-2455.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Greenberg H. B., Clark H. F., Offit P. A. Rotavirus pathology and pathophysiology. Curr Top Microbiol Immunol. 1994;185:255–283. doi: 10.1007/978-3-642-78256-5_9. [DOI] [PubMed] [Google Scholar]
  7. Hoshino Y., Saif L. J., Kang S. Y., Sereno M. M., Chen W. K., Kapikian A. Z. Identification of group A rotavirus genes associated with virulence of a porcine rotavirus and host range restriction of a human rotavirus in the gnotobiotic piglet model. Virology. 1995 May 10;209(1):274–280. doi: 10.1006/viro.1995.1255. [DOI] [PubMed] [Google Scholar]
  8. López S., Arias C. F. Sequence analysis of rotavirus YM VP6 and NS28 proteins. J Gen Virol. 1993 Jun;74(Pt 6):1223–1226. doi: 10.1099/0022-1317-74-6-1223. [DOI] [PubMed] [Google Scholar]
  9. Offit P. A., Blavat G., Greenberg H. B., Clark H. F. Molecular basis of rotavirus virulence: role of gene segment 4. J Virol. 1986 Jan;57(1):46–49. doi: 10.1128/jvi.57.1.46-49.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Okada Y., Richardson M. A., Ikegami N., Nomoto A., Furuichi Y. Nucleotide sequence of human rotavirus genome segment 10, an RNA encoding a glycosylated virus protein. J Virol. 1984 Sep;51(3):856–859. doi: 10.1128/jvi.51.3.856-859.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Osborne M. P., Haddon S. J., Spencer A. J., Collins J., Starkey W. G., Wallis T. S., Clarke G. J., Worton K. J., Candy D. C., Stephen J. An electron microscopic investigation of time-related changes in the intestine of neonatal mice infected with murine rotavirus. J Pediatr Gastroenterol Nutr. 1988 Mar-Apr;7(2):236–248. doi: 10.1097/00005176-198803000-00014. [DOI] [PubMed] [Google Scholar]
  12. Ramig R. F. The effects of host age, virus dose, and virus strain on heterologous rotavirus infection of suckling mice. Microb Pathog. 1988 Mar;4(3):189–202. doi: 10.1016/0882-4010(88)90069-1. [DOI] [PubMed] [Google Scholar]
  13. Shaw R. D., Hempson S. J., Mackow E. R. Rotavirus diarrhea is caused by nonreplicating viral particles. J Virol. 1995 Oct;69(10):5946–5950. doi: 10.1128/jvi.69.10.5946-5950.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ushijima H., Koike H., Mukoyama A., Hasegawa A., Nishimura S., Gentsch J. Detection and serotyping of rotaviruses in stool specimens by using reverse transcription and polymerase chain reaction amplification. J Med Virol. 1992 Dec;38(4):292–297. doi: 10.1002/jmv.1890380412. [DOI] [PubMed] [Google Scholar]
  15. Ward C. W., Azad A. A., Dyall-Smith M. L. Structural homologies between RNA gene segments 10 and 11 from UK bovine, simian SA11, and human Wa rotaviruses. Virology. 1985 Jul 30;144(2):328–336. doi: 10.1016/0042-6822(85)90275-2. [DOI] [PubMed] [Google Scholar]
  16. Ward R. L., Bernstein D. I., Young E. C., Sherwood J. R., Knowlton D. R., Schiff G. M. Human rotavirus studies in volunteers: determination of infectious dose and serological response to infection. J Infect Dis. 1986 Nov;154(5):871–880. doi: 10.1093/infdis/154.5.871. [DOI] [PubMed] [Google Scholar]
  17. Ward R. L., Sander D. S., Schiff G. M., Bernstein D. I. Effect of vaccination on serotype-specific antibody responses in infants administered WC3 bovine rotavirus before or after a natural rotavirus infection. J Infect Dis. 1990 Dec;162(6):1298–1303. doi: 10.1093/infdis/162.6.1298. [DOI] [PubMed] [Google Scholar]
  18. Wolf J. L., Cukor G., Blacklow N. R., Dambrauskas R., Trier J. S. Susceptibility of mice to rotavirus infection: effects of age and administration of corticosteroids. Infect Immun. 1981 Aug;33(2):565–574. doi: 10.1128/iai.33.2.565-574.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]

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