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Murine rotavirus genes encoding outer capsid proteins VP4 and VP7 are not major determinants of host range
1Veterinary Medical Unit, Veterans Affairs Medical Center, Palo Alto, California 94304.
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.
Insights
Simian rotavirus (RRV) and murine rotavirus (EDIM-RW) exhibit distinct disease patterns in mice. Genes 4 and 7 (VP4 and VP7) from RRV did not determine virulence or host range in this murine rotavirus model.
Area of Science:
- Virology
- Molecular Biology
- Infectious Diseases
Background:
- Simian rotavirus (RRV) and murine rotavirus (EDIM-RW) show significant differences in virulence and transmission in neonatal mice.
- Understanding the genetic basis of these differences is crucial for controlling rotavirus infections.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the differing virulence and host range of RRV and EDIM-റW in a neonatal mouse model.
- To identify specific viral genes responsible for these phenotypic variations.
Main Methods:
- Generation of reassortant rotaviruses by coinfecting infant mice with RRV and EDIM-RW.
- Isolation and plaque purification of reassortant viruses from infected mouse intestines.
- Evaluation of reassortants for 50% diarrhea dose (DD50) and transmission efficiency to uninoculated littermates.
Main Results:
- Parental RRV had a high DD50 (10^5 PFU/animal) and did not spread, while EDIM-RW had a low DD50 (<1 PFU/animal) and spread efficiently.
- Reassortants D1/5 and C3/2, possessing RRV genes 4 (VP4) and 7 (VP7), exhibited EDIM-RW-like low DD50 and efficient spread.
- These findings indicate that VP4 and VP7 are not the primary determinants of virulence or host range restriction in this homologous murine rotavirus model.
Conclusions:
- The major outer capsid proteins VP4 and VP7 are not primarily responsible for the observed differences in virulence and host range between RRV and EDIM-RW in mice.
- Further research is needed to identify other viral genes contributing to the distinct pathogenic properties of these rotaviruses.