Abstract
Simian rotavirus (RRV) and murine rotavirus (EDIM-RW) differ dramatically in the oral inoculum required to cause diarrheal disease in neonatal mouse pups and in their ability to spread and cause disease in uninoculated littermates. A genetic approach was used to explore the molecular basis of these differences. Reassortant viruses were produced in vivo by coinfecting infant mice with RRV and EDIM-RW. Reassortant viruses were isolated by plaque purification of progeny virus obtained from mouse pup intestines on MA104 cells. The plaque-purified reassortants were evaluated for 50% diarrhea dose (DD50) and for the ability to spread and cause diarrhea in uninoculated littermates. The parental RRV strain had a DD50 of 10(5) PFU per animal, while the EDIM-RW parental strain had a DD50 of less than 1 PFU per animal. RRV never spreads from inoculated to uninoculated littermates and causes disease. Twenty-three reassortants were tested. Of great interest were the reassortants D1/5 and C3/2, which derived genes 4 and 7 (encoding VP4 and VP7) from RRV. These viruses had a DD50 similar or identical to that of EDIM-RW and spread efficiently from inoculated mouse pups to uninoculated pups. We conclude that the major outer capsid proteins VP4 and VP7 are not primarily responsible for virulence or host range restriction in the mouse model using a homologous murine rotavirus.
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- Bass D. M., Baylor M., Broome R., Greenberg H. B. Molecular basis of age-dependent gastric inactivation of rhesus rotavirus in the mouse. J Clin Invest. 1992 Jun;89(6):1741–1745. doi: 10.1172/JCI115776. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bass D. M., Mackow E. R., Greenberg H. B. Identification and partial characterization of a rhesus rotavirus binding glycoprotein on murine enterocytes. Virology. 1991 Aug;183(2):602–610. doi: 10.1016/0042-6822(91)90989-o. [DOI] [PubMed] [Google Scholar]
- Bass D. M., Mackow E. R., Greenberg H. B. NS35 and not vp7 is the soluble rotavirus protein which binds to target cells. J Virol. 1990 Jan;64(1):322–330. doi: 10.1128/jvi.64.1.322-330.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bell L. M., Clark H. F., O'Brien E. A., Kornstein M. J., Plotkin S. A., Offit P. A. Gastroenteritis caused by human rotaviruses (serotype three) in a suckling mouse model. Proc Soc Exp Biol Med. 1987 Jan;184(1):127–132. doi: 10.3181/00379727-184-rc2. [DOI] [PubMed] [Google Scholar]
- Blacklow N. R., Greenberg H. B. Viral gastroenteritis. N Engl J Med. 1991 Jul 25;325(4):252–264. doi: 10.1056/NEJM199107253250406. [DOI] [PubMed] [Google Scholar]
- Bodkin D. K., Fields B. N. Growth and survival of reovirus in intestinal tissue: role of the L2 and S1 genes. J Virol. 1989 Mar;63(3):1188–1193. doi: 10.1128/jvi.63.3.1188-1193.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen D. Y., Estes M. K., Ramig R. F. Specific interactions between rotavirus outer capsid proteins VP4 and VP7 determine expression of a cross-reactive, neutralizing VP4-specific epitope. J Virol. 1992 Jan;66(1):432–439. doi: 10.1128/jvi.66.1.432-439.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen D., Burns J. W., Estes M. K., Ramig R. F. Phenotypes of rotavirus reassortants depend upon the recipient genetic background. Proc Natl Acad Sci U S A. 1989 May;86(10):3743–3747. doi: 10.1073/pnas.86.10.3743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark H. F., Borian F. E., Plotkin S. A. Immune protection of infants against rotavirus gastroenteritis by a serotype 1 reassortant of bovine rotavirus WC3. J Infect Dis. 1990 Jun;161(6):1099–1104. doi: 10.1093/infdis/161.6.1099. [DOI] [PubMed] [Google Scholar]
- Dharakul T., Rott L., Greenberg H. B. Recovery from chronic rotavirus infection in mice with severe combined immunodeficiency: virus clearance mediated by adoptive transfer of immune CD8+ T lymphocytes. J Virol. 1990 Sep;64(9):4375–4382. doi: 10.1128/jvi.64.9.4375-4382.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dunn S. J., Greenberg H. B., Ward R. L., Nakagomi O., Burns J. W., Vo P. T., Pax K. A., Das M., Gowda K., Rao C. D. Serotypic and genotypic characterization of human serotype 10 rotaviruses from asymptomatic neonates. J Clin Microbiol. 1993 Jan;31(1):165–169. doi: 10.1128/jcm.31.1.165-169.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Estes M. K., Cohen J. Rotavirus gene structure and function. Microbiol Rev. 1989 Dec;53(4):410–449. doi: 10.1128/mr.53.4.410-449.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flores J., Perez-Schael I., Blanco M., White L., Garcia D., Vilar M., Cunto W., Gonzalez R., Urbina C., Boher J. Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus-rotavirus-based quadrivalent vaccine. Lancet. 1990 Aug 11;336(8711):330–334. doi: 10.1016/0140-6736(90)91876-c. [DOI] [PubMed] [Google Scholar]
- Flores J., Perez-Schael I., Gonzalez M., Garcia D., Perez M., Daoud N., Cunto W., Chanock R. M., Kapikian A. Z. Protection against severe rotavirus diarrhoea by rhesus rotavirus vaccine in Venezuelan infants. Lancet. 1987 Apr 18;1(8538):882–884. doi: 10.1016/s0140-6736(87)92858-3. [DOI] [PubMed] [Google Scholar]
- Fukuhara N., Yoshie O., Kitaoka S., Konno T. Role of VP3 in human rotavirus internalization after target cell attachment via VP7. J Virol. 1988 Jul;62(7):2209–2218. doi: 10.1128/jvi.62.7.2209-2218.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gallegos C. O., Patton J. T. Characterization of rotavirus replication intermediates: a model for the assembly of single-shelled particles. Virology. 1989 Oct;172(2):616–627. doi: 10.1016/0042-6822(89)90204-3. [DOI] [PubMed] [Google Scholar]
- Gerna G., Sarasini A., Di Matteo A., Zentilin L., Miranda P., Parea M., Baldanti F., Arista S., Milanesi G., Battaglia M. Serotype 3 human rotavirus strains with subgroup I specificity. J Clin Microbiol. 1990 Jun;28(6):1342–1347. doi: 10.1128/jcm.28.6.1342-1347.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gombold J. L., Ramig R. F. Analysis of reassortment of genome segments in mice mixedly infected with rotaviruses SA11 and RRV. J Virol. 1986 Jan;57(1):110–116. doi: 10.1128/jvi.57.1.110-116.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gorziglia M., Green K., Nishikawa K., Taniguchi K., Jones R., Kapikian A. Z., Chanock R. M. Sequence of the fourth gene of human rotaviruses recovered from asymptomatic or symptomatic infections. J Virol. 1988 Aug;62(8):2978–2984. doi: 10.1128/jvi.62.8.2978-2984.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham A., Kudesia G., Allen A. M., Desselberger U. Reassortment of human rotavirus possessing genome rearrangements with bovine rotavirus: evidence for host cell selection. J Gen Virol. 1987 Jan;68(Pt 1):115–122. doi: 10.1099/0022-1317-68-1-115. [DOI] [PubMed] [Google Scholar]
- Greenberg H. B., Kalica A. R., Wyatt R. G., Jones R. W., Kapikian A. Z., Chanock R. M. Rescue of noncultivatable human rotavirus by gene reassortment during mixed infection with ts mutants of a cultivatable bovine rotavirus. Proc Natl Acad Sci U S A. 1981 Jan;78(1):420–424. doi: 10.1073/pnas.78.1.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenberg H. B., Valdesuso J., van Wyke K., Midthun K., Walsh M., McAuliffe V., Wyatt R. G., Kalica A. R., Flores J., Hoshino Y. Production and preliminary characterization of monoclonal antibodies directed at two surface proteins of rhesus rotavirus. J Virol. 1983 Aug;47(2):267–275. doi: 10.1128/jvi.47.2.267-275.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenberg H. B., Vo P. T., Jones R. Cultivation and characterization of three strains of murine rotavirus. J Virol. 1986 Feb;57(2):585–590. doi: 10.1128/jvi.57.2.585-590.1986. [DOI] [PMC free article] [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., 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., Midthun K., Gorziglia M., Green K. Y., Chanock R. M., Potash L., Sears S. D., Clements M. L. Prospects for development of a rotavirus vaccine against rotavirus diarrhea in infants and young children. Rev Infect Dis. 1989 May-Jun;11 (Suppl 3):S539–S546. doi: 10.1093/clinids/11.supplement_3.s539. [DOI] [PubMed] [Google Scholar]
- Lanata C. F., Black R. E., del Aguila R., Gil A., Verastegui H., Gerna G., Flores J., Kapikian A. Z., Andre F. E. Protection of Peruvian children against rotavirus diarrhea of specific serotypes by one, two, or three doses of the RIT 4237 attenuated bovine rotavirus vaccine. J Infect Dis. 1989 Mar;159(3):452–459. doi: 10.1093/infdis/159.3.452. [DOI] [PubMed] [Google Scholar]
- Mackow E. R., Barnett J. W., Chan H., Greenberg H. B. The rhesus rotavirus outer capsid protein VP4 functions as a hemagglutinin and is antigenically conserved when expressed by a baculovirus recombinant. J Virol. 1989 Apr;63(4):1661–1668. doi: 10.1128/jvi.63.4.1661-1668.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mansell E. A., Patton J. T. Rotavirus RNA replication: VP2, but not VP6, is necessary for viral replicase activity. J Virol. 1990 Oct;64(10):4988–4996. doi: 10.1128/jvi.64.10.4988-4996.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsui S. M., Offit P. A., Vo P. T., Mackow E. R., Benfield D. A., Shaw R. D., Padilla-Noriega L., Greenberg H. B. Passive protection against rotavirus-induced diarrhea by monoclonal antibodies to the heterotypic neutralization domain of VP7 and the VP8 fragment of VP4. J Clin Microbiol. 1989 Apr;27(4):780–782. doi: 10.1128/jcm.27.4.780-782.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakagomi O., Ohshima A., Aboudy Y., Shif I., Mochizuki M., Nakagomi T., Gotlieb-Stematsky T. Molecular identification by RNA-RNA hybridization of a human rotavirus that is closely related to rotaviruses of feline and canine origin. J Clin Microbiol. 1990 Jun;28(6):1198–1203. doi: 10.1128/jcm.28.6.1198-1203.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nishikawa K., Hoshino Y., Taniguchi K., Green K. Y., Greenberg H. B., Kapikian A. Z., Chanock R. M., Gorziglia M. Rotavirus VP7 neutralization epitopes of serotype 3 strains. Virology. 1989 Aug;171(2):503–515. doi: 10.1016/0042-6822(89)90620-x. [DOI] [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., Clark H. F., Kornstein M. J., Plotkin S. A. A murine model for oral infection with a primate rotavirus (simian SA11). J Virol. 1984 Jul;51(1):233–236. doi: 10.1128/jvi.51.1.233-236.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Offit P. A., Clark H. F. Protection against rotavirus-induced gastroenteritis in a murine model by passively acquired gastrointestinal but not circulating antibodies. J Virol. 1985 Apr;54(1):58–64. doi: 10.1128/jvi.54.1.58-64.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Offit P. A., Dudzik K. I. Rotavirus-specific cytotoxic T lymphocytes passively protect against gastroenteritis in suckling mice. J Virol. 1990 Dec;64(12):6325–6328. doi: 10.1128/jvi.64.12.6325-6328.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patton J. T., Gallegos C. O. Rotavirus RNA replication: single-stranded RNA extends from the replicase particle. J Gen Virol. 1990 May;71(Pt 5):1087–1094. doi: 10.1099/0022-1317-71-5-1087. [DOI] [PubMed] [Google Scholar]
- Ramig R. F., Galle K. L. Rotavirus genome segment 4 determines viral replication phenotype in cultured liver cells (HepG2). J Virol. 1990 Mar;64(3):1044–1049. doi: 10.1128/jvi.64.3.1044-1049.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sabara M., Gilchrist J. E., Hudson G. R., Babiuk L. A. Preliminary characterization of an epitope involved in neutralization and cell attachment that is located on the major bovine rotavirus glycoprotein. J Virol. 1985 Jan;53(1):58–66. doi: 10.1128/jvi.53.1.58-66.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Santosham M., Letson G. W., Wolff M., Reid R., Gahagan S., Adams R., Callahan C., Sack R. B., Kapikian A. Z. A field study of the safety and efficacy of two candidate rotavirus vaccines in a Native American population. J Infect Dis. 1991 Mar;163(3):483–487. doi: 10.1093/infdis/163.3.483. [DOI] [PubMed] [Google Scholar]
- Shaw R. D., Stoner-Ma D. L., Estes M. K., Greenberg H. B. Specific enzyme-linked immunoassay for rotavirus serotypes 1 and 3. J Clin Microbiol. 1985 Aug;22(2):286–291. doi: 10.1128/jcm.22.2.286-291.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sherry B., Fields B. N. The reovirus M1 gene, encoding a viral core protein, is associated with the myocarditic phenotype of a reovirus variant. J Virol. 1989 Nov;63(11):4850–4856. doi: 10.1128/jvi.63.11.4850-4856.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ward R. L., McNeal M. M., Sheridan J. F. Development of an adult mouse model for studies on protection against rotavirus. J Virol. 1990 Oct;64(10):5070–5075. doi: 10.1128/jvi.64.10.5070-5075.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]