MECHANIHMB OF INTESTINAL IMMUNITY TO ROTAVIRUS ENTERITIS: CHARACTERISTICS OF PERSISTENT INFECTION IN SEVERE COMBINED IMMUNODEFICIENT (SCID) MICE

Abstract

Using ELISA and fluorescent antibody assays, we followed shedding and replication of mouse rotavirus (MRV) in groups of suckling, adult, and lactating female SCID, and age matched normal (control) mice. The mice were infected, with orally administered live MRV, or spontaneously via ingestion of virus containing feces from infected pups. Suckling normal and SCID mice were infected with MRV with development of disease in a predictable manner. However, SCID infants exhibited more severe disease and persistent viral shedding in the feces. Although normal adult mice could not be infected with the virus, SCID adults developed infection in about 5-10% of villous enterocytes, but with little or no clinical disease, significantly, these animals continued to shed virus in feces intermittently 4 to 5 months (to date) after primary infection. No MRV specific secretory antibody activity was induced in the intestine in SCID mice. However, such infected adults manifested significant resistance to subsequent attempts at reinfection with high dose of virus (8×105 ID50) administered orally. The virus recovered from the SCID mice was highly infectious when re-inoculated in susceptible suckling animals. These data suggest that the virus and host may have achieved a “steady state” in the gut in immunodeficient animals, implying that factors other than rotavirus-specific serum and secretory antibody or T cell function are important in controlling virus replication in the gut.