Murine rotavirus genes encoding outer capsid proteins VP4 and VP7 are not major determinants of host range restriction and virulence.
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.
Veterinary Medical Unit, Veterans Affairs Medical Center, Palo Alto, California 94304.
R L
RL
Broome
P T
PT
Vo
R L
RL
Ward
H F
HF
Clark
H B
HB
Greenberg
D000818:Animals; D000833:Animals, Suckling; D000956:Antigens, Viral; D002213:Capsid / Q000235:genetics*; D036022:Capsid Proteins; D003967:Diarrhea / Q000209:etiology / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D005814:Genes, Viral / Q000235:genetics*; D005838:Genotype; D007422:Intestines / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D011995:Recombination, Genetic; D012401:Rotavirus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D013045:Species Specificity; D010948:Viral Plaque Assay; D014774:Virulence / Q000235:genetics; D014779:Virus Replication; D017201:Virus Shedding
D000956:Antigens, Viral; D036022:Capsid Proteins; C060339:VP4 protein, Rotavirus; C050779:VP7 protein, Rotavirus