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.
Mossel
Eric C
EC
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
Ramig
Robert F
RF
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