A lymphatic mechanism of rotavirus extraintestinal spread in the neonatal mouse.
We used the neonatal mouse model of rotavirus infection and virus strains SA11-clone 4 (SA11-Cl4) and Rhesus rotavirus (RRV) to examine the mechanism of the extraintestinal spread of viruses following oral inoculation. The spread-competent viruses, RRV and reassortant R7, demonstrated a temporal progression from the intestine, to the terminal ileum, to the mesenteric lymph nodes (MLN), and to the peripheral tissues. SA11-Cl4 was not found outside the intestine. Reassortant virus S7, which was unable to reach the liver in previous studies (E. C. Mossel and R. F. Ramig, J. Virol. 76:6502-6509, 2002), was recovered from 60% of the MLN, suggesting that there are multiple determinants for the spread of virus from the intestine to the MLN. Phenotypic segregation analysis identified RRV genome segment 6 (VP6) as a secondary determinant of the spread of virus to the MLN (P = 0.02) in reassortant viruses containing segment 7 from the spread-incompetent parent. These data suggest that in the orally infected neonatal mouse, the extraintestinal spread of rotavirus occurs via a lymphatic pathway, and the spread phenotype is primarily determined by NSP3 and can be modified by VP6.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
Eric C
EC
Mossel
Robert F
RF
Ramig
D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral; D036022:Capsid Proteins / Q000502:physiology; D007422:Intestines / Q000821:virology; D008198:Lymph Nodes / Q000821:virology*; D051379:Mice; D012401:Rotavirus / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000502:physiology
D000956:Antigens, Viral; D036022:Capsid Proteins; C082740:NSP3 protein, Rotavirus; C061332:VP6 protein, Rotavirus; D017361:Viral Nonstructural Proteins