Abstract
Within the past few years, rotavirus strains were recovered from four discrete prolonged outbreaks of infection in newborn nurseries in which affected infants failed to develop significant symptoms. The virus strains recovered from each outbreak belonged to a different human rotavirus serotype and thus each of the four human rotavirus serotypes was associated with asymptomatic infection of neonates. Marked conservation of sequence was observed among the fourth genes of the nursery rotavirus strains in a previous study using RNA X RNA hybridization, while a different conserved set of fourth gene sequences was identified among virulent human rotaviruses representing the four known serotypes. In the present study, this sequence dimorphism was further evaluated by comparing the sequence of the region of the fourth gene of virulent and asymptomatic human rotaviruses that codes for the VP8 protein, downstream cleavage sites, and the NH2 terminus of VP5. The corresponding sequences of a simian rotavirus were also determined. The fourth segment (+) strand RNA has a 5' conserved nontranslated sequence of nine nucleotides and encodes a VP8 protein of 240 amino acids in human rotavirus strains and 241 amino acids in simian rotavirus strains. Human and simian rotaviruses exhibit many similarities in this region of their genome, including identical NH2-terminal amino acid sequences, conservation of arginine at the two trypsin cleavage sites, and the position of a cysteine residue. Alignment of amino acid sequences of the VP8 protein, the downstream cleavage region, and the NH2 terminus of VP5 of asymptomatic and virulent human rotavirus strains indicates a high degree of homology (96% or more) among the asymptomatic viruses (serotypes 1, 2, 3, and 4), while homology between asymptomatic strains and virulent viruses is considerably less (68-72%). A high degree of conservation of amino acid sequence (92-97%) is also observed among three of the virulent strains (serotypes 1, 3, and 4). At 48 positions in the protein sequence of VP8, the cleavage region, and the NH2 terminus of VP5, an amino acid is conserved among asymptomatic rotaviruses, while a different amino acid is conserved among virulent rotaviruses. Notably, three of these differences are located within the cleavage region between VP8 and VP5. These findings suggest that the fourth genes of virulent and asymptomatic human rotavirus strains represent two lines of divergent evolution from a common ancestor. Also, it is possible that this sequence dimorphism may be responsible in part for the difference in virulence between these two groups of human rotaviruses.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bryden A. S., Thouless M. E., Hall C. J., Flewett T. H., Wharton B. A., Mathew P. M., Craig I. Rotavirus infections in a special-care baby unit. J Infect. 1982 Jan;4(1):43–48. doi: 10.1016/s0163-4453(82)90988-4. [DOI] [PubMed] [Google Scholar]
- Ericson B. L., Graham D. Y., Mason B. B., Estes M. K. Identification, synthesis, and modifications of simian rotavirus SA11 polypeptides in infected cells. J Virol. 1982 Jun;42(3):825–839. doi: 10.1128/jvi.42.3.825-839.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Esparza J., Gorziglia M., Gil F., Römer H. Multiplication of human rotavirus in cultured cells: an electron microscopic study. J Gen Virol. 1980 Apr;47(2):461–472. doi: 10.1099/0022-1317-47-2-461. [DOI] [PubMed] [Google Scholar]
- Espejo R. T., López S., Arias C. Structural polypeptides of simian rotavirus SA11 and the effect of trypsin. J Virol. 1981 Jan;37(1):156–160. doi: 10.1128/jvi.37.1.156-160.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Estes M. K., Graham D. Y., Mason B. B. Proteolytic enhancement of rotavirus infectivity: molecular mechanisms. J Virol. 1981 Sep;39(3):879–888. doi: 10.1128/jvi.39.3.879-888.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flores J., Greenberg H. B., Myslinski J., Kalica A. R., Wyatt R. G., Kapikian A. Z., Chanock R. M. Use of transcription probes for genotyping rotavirus reassortants. Virology. 1982 Sep;121(2):288–295. doi: 10.1016/0042-6822(82)90168-4. [DOI] [PubMed] [Google Scholar]
- Flores J., Greenberg H. B., Myslinski J., Kalica A. R., Wyatt R. G., Kapikian A. Z., Chanock R. M. Use of transcription probes for genotyping rotavirus reassortants. Virology. 1982 Sep;121(2):288–295. doi: 10.1016/0042-6822(82)90168-4. [DOI] [PubMed] [Google Scholar]
- Flores J., Perez I., White L., Perez M., Kalica A. R., Marquina R., Wyatt R. G., Kapikian A. Z., Chanock R. M. Genetic relatedness among human rotaviruses as determined by RNA hybridization. Infect Immun. 1982 Aug;37(2):648–655. doi: 10.1128/iai.37.2.648-655.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenberg H. B., Flores J., Kalica A. R., Wyatt R. G., Jones R. Gene coding assignments for growth restriction, neutralization and subgroup specificities of the W and DS-1 strains of human rotavirus. J Gen Virol. 1983 Feb;64(Pt 2):313–320. doi: 10.1099/0022-1317-64-2-313. [DOI] [PubMed] [Google Scholar]
- Hoshino Y., Sereno M. M., Midthun K., Flores J., Kapikian A. Z., Chanock R. M. Independent segregation of two antigenic specificities (VP3 and VP7) involved in neutralization of rotavirus infectivity. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8701–8704. doi: 10.1073/pnas.82.24.8701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoshino Y., Wyatt R. G., Flores J., Midthun K., Kapikian A. Z. Serotypic characterization of rotaviruses derived from asymptomatic human neonatal infections. J Clin Microbiol. 1985 Mar;21(3):425–430. doi: 10.1128/jcm.21.3.425-430.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoshino Y., Wyatt R. G., Greenberg H. B., Flores J., Kapikian A. Z. Serotypic similarity and diversity of rotaviruses of mammalian and avian origin as studied by plaque-reduction neutralization. J Infect Dis. 1984 May;149(5):694–702. doi: 10.1093/infdis/149.5.694. [DOI] [PubMed] [Google Scholar]
- Kalica A. R., Flores J., Greenberg H. B. Identification of the rotaviral gene that codes for hemagglutination and protease-enhanced plaque formation. Virology. 1983 Feb;125(1):194–205. doi: 10.1016/0042-6822(83)90073-9. [DOI] [PubMed] [Google Scholar]
- Kapikian A. Z., Flores J., Hoshino Y., Glass R. I., Midthun K., Gorziglia M., Chanock R. M. Rotavirus: the major etiologic agent of severe infantile diarrhea may be controllable by a "Jennerian" approach to vaccination. J Infect Dis. 1986 May;153(5):815–822. doi: 10.1093/infdis/153.5.815. [DOI] [PubMed] [Google Scholar]
- Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
- Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
- López S., Arias C. F., Bell J. R., Strauss J. H., Espejo R. T. Primary structure of the cleavage site associated with trypsin enhancement of rotavirus SA11 infectivity. Virology. 1985 Jul 15;144(1):11–19. doi: 10.1016/0042-6822(85)90300-9. [DOI] [PubMed] [Google Scholar]
- Mason B. B., Graham D. Y., Estes M. K. Biochemical mapping of the simian rotavirus SA11 genome. J Virol. 1983 May;46(2):413–423. doi: 10.1128/jvi.46.2.413-423.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Offit P. A., Blavat G. Identification of the two rotavirus genes determining neutralization specificities. J Virol. 1986 Jan;57(1):376–378. doi: 10.1128/jvi.57.1.376-378.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Offit P. A., Clark H. F., Stroop W. G., Twist E. M., Plotkin S. A. The cultivation of human rotavirus, strain 'Wa', to high titer in cell culture and characterization of the viral structural polypeptides. J Virol Methods. 1983 Jul;7(1):29–40. doi: 10.1016/0166-0934(83)90020-4. [DOI] [PubMed] [Google Scholar]
- Sato K., Inaba Y., Shinozaki T., Fujii R., Matumoto M. Isolation of human rotavirus in cell cultures: brief report. Arch Virol. 1981;69(2):155–160. doi: 10.1007/BF01315159. [DOI] [PubMed] [Google Scholar]
- Urasawa T., Urasawa S., Taniguchi K. Sequential passages of human rotavirus in MA-104 cells. Microbiol Immunol. 1981;25(10):1025–1035. doi: 10.1111/j.1348-0421.1981.tb00109.x. [DOI] [PubMed] [Google Scholar]
- Wyatt R. G., Gill V. W., Sereno M. M., Kalica A. R., VanKirk D. H., Chanock R. M., Kapikian A. Z. Letter: Probable in-vitro cultivation of human reovirus-like agent of infantile diarroea. Lancet. 1976 Jan 10;1(7950):98–99. doi: 10.1016/s0140-6736(76)90202-6. [DOI] [PubMed] [Google Scholar]