Abstract
Mutants of mammalian reoviruses, enteric double-stranded-RNA-containing viruses that spread systemically after primary replication in intestinal tissue, have been extensively studied as models of viral pathogenesis. While reovirus serotype 3 strain Dearing (T3D) causes acute encephalitis in newborn mice, adult severe combined immunodeficient (SCID) mice develop chronic infection with T3D, with some mice living more than 100 days after infection (B. L. Haller, M. L. Barkon, G. P. Vogler, and H. W. Virgin IV, J. Virol. 69:357-364, 1995). To determine whether organ-specific reovirus variants are selected during chronic infection, we characterized the pathogenetic properties of two variants of T3D isolated 87 days after intraperitoneal infection of adult SCID mice. A brain-specific variant (T3DvBr) (i) grew to a higher titer than T3D in SCID mouse brain (but not intestine) after intraperitoneal inoculation, (ii) killed adult SCID mice faster than T3D, and (iii) grew well in neonatal NIH Swiss [NIH(s)] mouse brain tissue after intramuscular but not peroral inoculation. An intestine-specific variant (T3DvInt) (i) grew to a higher titer than T3D in SCID mouse intestine (but not brain) after intraperitoneal inoculation, (ii) killed SCID mice with kinetics equivalent to those of T3D, (iii) was much less virulent than T3D in neonatal NIH(s) mice, (iv) grew better than T3D in intestines after intramuscular or peroral inoculation into neonatal NIH(s) mice, and (v) grew poorly in brain tissue of neonatal NIH(s) mice after intramuscular inoculation. During prolonged infection of SCID mice, organ-specific variants of T3D, which are more efficient than wild-type T3D at one specific stage in reovirus pathogenesis, are selected.
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- Ahmed R., Canning W. M., Kauffman R. S., Sharpe A. H., Hallum J. V., Fields B. N. Role of the host cell in persistent viral infection: coevolution of L cells and reovoirus during persistent infection. Cell. 1981 Aug;25(2):325–332. doi: 10.1016/0092-8674(81)90050-7. [DOI] [PubMed] [Google Scholar]
- Ahmed R., Fields B. N. Role of the S4 gene in the establishment of persistent reovirus infection in L cells. Cell. 1982 Mar;28(3):605–612. doi: 10.1016/0092-8674(82)90215-x. [DOI] [PubMed] [Google Scholar]
- Ahmed R., Oldstone M. B. Organ-specific selection of viral variants during chronic infection. J Exp Med. 1988 May 1;167(5):1719–1724. doi: 10.1084/jem.167.5.1719. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bassel-Duby R., Spriggs D. R., Tyler K. L., Fields B. N. Identification of attenuating mutations on the reovirus type 3 S1 double-stranded RNA segment with a rapid sequencing technique. J Virol. 1986 Oct;60(1):64–67. doi: 10.1128/jvi.60.1.64-67.1986. [DOI] [PMC free article] [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]
- Burstin S. J., Spriggs D. R., Fields B. N. Evidence for functional domains on the reovirus type 3 hemagglutinin. Virology. 1982 Feb;117(1):146–155. doi: 10.1016/0042-6822(82)90514-1. [DOI] [PubMed] [Google Scholar]
- Dermody T. S., Nibert M. L., Wetzel J. D., Tong X., Fields B. N. Cells and viruses with mutations affecting viral entry are selected during persistent infections of L cells with mammalian reoviruses. J Virol. 1993 Apr;67(4):2055–2063. doi: 10.1128/jvi.67.4.2055-2063.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dryden K. A., Wang G., Yeager M., Nibert M. L., Coombs K. M., Furlong D. B., Fields B. N., Baker T. S. Early steps in reovirus infection are associated with dramatic changes in supramolecular structure and protein conformation: analysis of virions and subviral particles by cryoelectron microscopy and image reconstruction. J Cell Biol. 1993 Sep;122(5):1023–1041. doi: 10.1083/jcb.122.5.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- George A., Kost S. I., Witzleben C. L., Cebra J. J., Rubin D. H. Reovirus-induced liver disease in severe combined immunodeficient (SCID) mice. A model for the study of viral infection, pathogenesis, and clearance. J Exp Med. 1990 Mar 1;171(3):929–934. doi: 10.1084/jem.171.3.929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gombold J. L., Ramig R. F. Passive immunity modulates genetic reassortment between rotaviruses in mixedly infected mice. J Virol. 1989 Nov;63(11):4525–4532. doi: 10.1128/jvi.63.11.4525-4532.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haller B. L., Barkon M. L., Vogler G. P., Virgin H. W., 4th Genetic mapping of reovirus virulence and organ tropism in severe combined immunodeficient mice: organ-specific virulence genes. J Virol. 1995 Jan;69(1):357–364. doi: 10.1128/jvi.69.1.357-364.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaye K. M., Spriggs D. R., Bassel-Duby R., Fields B. N., Tyler K. L. Genetic basis for altered pathogenesis of an immune-selected antigenic variant of reovirus type 3 (Dearing). J Virol. 1986 Jul;59(1):90–97. doi: 10.1128/jvi.59.1.90-97.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- King C. C., de Fries R., Kolhekar S. R., Ahmed R. In vivo selection of lymphocyte-tropic and macrophage-tropic variants of lymphocytic choriomeningitis virus during persistent infection. J Virol. 1990 Nov;64(11):5611–5616. doi: 10.1128/jvi.64.11.5611-5616.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levine B., Griffin D. E. Molecular analysis of neurovirulent strains of Sindbis virus that evolve during persistent infection of scid mice. J Virol. 1993 Nov;67(11):6872–6875. doi: 10.1128/jvi.67.11.6872-6875.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lieber M. R., Hesse J. E., Lewis S., Bosma G. C., Rosenberg N., Mizuuchi K., Bosma M. J., Gellert M. The defect in murine severe combined immune deficiency: joining of signal sequences but not coding segments in V(D)J recombination. Cell. 1988 Oct 7;55(1):7–16. doi: 10.1016/0092-8674(88)90004-9. [DOI] [PubMed] [Google Scholar]
- Matloubian M., Somasundaram T., Kolhekar S. R., Selvakumar R., Ahmed R. Genetic basis of viral persistence: single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice. J Exp Med. 1990 Oct 1;172(4):1043–1048. doi: 10.1084/jem.172.4.1043. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morrison L. A., Fields B. N., Dermody T. S. Prolonged replication in the mouse central nervous system of reoviruses isolated from persistently infected cell cultures. J Virol. 1993 Jun;67(6):3019–3026. doi: 10.1128/jvi.67.6.3019-3026.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morrison L. A., Sidman R. L., Fields B. N. Direct spread of reovirus from the intestinal lumen to the central nervous system through vagal autonomic nerve fibers. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3852–3856. doi: 10.1073/pnas.88.9.3852. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramig R. F., Cross R. K., Fields B. N. Genome RNAs and polypeptides of reovirus serotypes 1, 2, and 3. J Virol. 1977 Jun;22(3):726–733. doi: 10.1128/jvi.22.3.726-733.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riepenhoff-Talty M., Dharakul T., Kowalski E., Michalak S., Ogra P. L. Persistent rotavirus infection in mice with severe combined immunodeficiency. J Virol. 1987 Oct;61(10):3345–3348. doi: 10.1128/jvi.61.10.3345-3348.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schuler W., Schuler A., Bosma M. J. Defective V-to-J recombination of T cell receptor gamma chain genes in scid mice. Eur J Immunol. 1990 Mar;20(3):545–550. doi: 10.1002/eji.1830200313. [DOI] [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]
- Sherry B., Li X. Y., Tyler K. L., Cullen J. M., Virgin H. W., 4th Lymphocytes protect against and are not required for reovirus-induced myocarditis. J Virol. 1993 Oct;67(10):6119–6124. doi: 10.1128/jvi.67.10.6119-6124.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sherry B., Schoen F. J., Wenske E., Fields B. N. Derivation and characterization of an efficiently myocarditic reovirus variant. J Virol. 1989 Nov;63(11):4840–4849. doi: 10.1128/jvi.63.11.4840-4849.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sturzenbecker L. J., Nibert M., Furlong D., Fields B. N. Intracellular digestion of reovirus particles requires a low pH and is an essential step in the viral infectious cycle. J Virol. 1987 Aug;61(8):2351–2361. doi: 10.1128/jvi.61.8.2351-2361.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tyler K. L., Mann M. A., Fields B. N., Virgin H. W., 4th Protective anti-reovirus monoclonal antibodies and their effects on viral pathogenesis. J Virol. 1993 Jun;67(6):3446–3453. doi: 10.1128/jvi.67.6.3446-3453.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tyler K. L., McPhee D. A., Fields B. N. Distinct pathways of viral spread in the host determined by reovirus S1 gene segment. Science. 1986 Aug 15;233(4765):770–774. doi: 10.1126/science.3016895. [DOI] [PubMed] [Google Scholar]
- Tyler K. L., Virgin H. W., 4th, Bassel-Duby R., Fields B. N. Antibody inhibits defined stages in the pathogenesis of reovirus serotype 3 infection of the central nervous system. J Exp Med. 1989 Sep 1;170(3):887–900. doi: 10.1084/jem.170.3.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Virgin H. W., 4th, Bassel-Duby R., Fields B. N., Tyler K. L. Antibody protects against lethal infection with the neurally spreading reovirus type 3 (Dearing). J Virol. 1988 Dec;62(12):4594–4604. doi: 10.1128/jvi.62.12.4594-4604.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Virgin H. W., 4th, Mann M. A., Fields B. N., Tyler K. L. Monoclonal antibodies to reovirus reveal structure/function relationships between capsid proteins and genetics of susceptibility to antibody action. J Virol. 1991 Dec;65(12):6772–6781. doi: 10.1128/jvi.65.12.6772-6781.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Virgin H. W., 4th, Mann M. A., Tyler K. L. Protective antibodies inhibit reovirus internalization and uncoating by intracellular proteases. J Virol. 1994 Oct;68(10):6719–6729. doi: 10.1128/jvi.68.10.6719-6729.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wenske E. A., Chanock S. J., Krata L., Fields B. N. Genetic reassortment of mammalian reoviruses in mice. J Virol. 1985 Nov;56(2):613–616. doi: 10.1128/jvi.56.2.613-616.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wessner D. R., Fields B. N. Isolation and genetic characterization of ethanol-resistant reovirus mutants. J Virol. 1993 May;67(5):2442–2447. doi: 10.1128/jvi.67.5.2442-2447.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zou S., Brown E. G. Identification of sequence elements containing signals for replication and encapsidation of the reovirus M1 genome segment. Virology. 1992 Feb;186(2):377–388. doi: 10.1016/0042-6822(92)90003-8. [DOI] [PubMed] [Google Scholar]