Susceptibility of mice to rotavirus infection: effects of age and administration of corticosteroids

Abstract

We examined susceptibility to the murine rotavirus, epizootic diarrhea of infant mice virus (EDIM), in normal suckling and weaned mice and in suckling mice treated with glucocorticoids. Normal mice 1 to 40 days old were inoculated by gastrin intubation with high doses of EDIM and subsequently evaluated for rotavirus infection by solid-phase radioimmunoassay, by electron microscopy of intestinal tissue sections or by both. Radioimmunoassay and electron microscopy showed a concordance of 89.5% in the detection of rotavirus infection. After a period of low susceptibility to EDIM infection during the first 3 days after birth (23%), susceptibility was high for the next 11 days (95%), but decreased abruptly as mice approached weaning (41% on days 15 through 17). Mice 34 days or older did not develop EDIM infection after inoculation, but rotavirus antigen was detected in 12% of uninoculated mothers nursing inoculated litters. Administration of cortisone acetate to 8-day-old mice induced partial intestinal maturation prematurely. At 3 to 6 days after cortisone acetate treatment, susceptibility to EDIM infection decreased to 60% compared with 94% in age-matched controls. Our data suggest (i) that susceptibility of mice to EDIM infection is age dependent, decreasing in concert with intestinal maturation, and (ii) that glucocorticoids, which induce premature partial intestinal maturation, modulate susceptibility of mice to EDIM.

Development of a murine model to study the pathogenesis of rotavirus infection

“…and with ! al., The results of the present study on the infection and replication of both homologous and heterologous rotavirus in a murine model confirm and extend the reports of others (Eydelloth et al, 1984;Gouvea et al, 1986;Kraft, 1982;Offrt et al, 1984;Ramig, 1988;Starkey et al, 1986;Wolf et al, 1981). However, our results differ from previous reports in several respects.…”

“…virus titer in intestinal tissue sample taken 1 HP1 never exceeded the ated virus dose which indicates that these isolates were undergoing the phases of replication cycle. This observation is consistent with prevj ious reports (Eydelloth et al, 1984;Gouvea et al, 1986;Kraft, 1982;Offrt et al, 191 64;Ramig, 1988;Starkey et al, 1986;Wolf et al, 1981). However, the peaks of infectious virus occurred earlier than in other studies, suggesting that the rate of replication of both the isolates is much faster than other human and animal ro 'tavirus isolates used in mouse models.…”

“…No such vaccine is yet available. In order to develop effective methods of prevention and control, efforts have been directed at developing animal models for rotavirus-induced diarrhea which would mimic human (6 months to 2 years) (Conner et al, 1988) and animal (< 1 month) (Eiden et al, 1986;Eydelloth et al, 1984;Gouvea et al, 1986;Otfit et al, 1984;Offor et al, 1985;Ramig, 1988;Riepenhoff-Talty et al, 1982;Starkey et al, 1986;Wolf et al, 1981) situations. In order to test rotavirus vaccines developed in our laboratory we have developed a murine model for murine rotavirus (MRV) and bovine rotavirus (BRV) infections, in which rotavirusinduced diarrhea can be produced in the first week of the neonate's life, thus mimicking the time when disease is prevalent in natural cases.…”

The effect of dexamethasone-induced immunosuppression on the development of faecal antibody and recovery from and resistance to rotavirus infection

“…However, one must also raise the caveat that DX can affect a variety of immunological and physiological processes other than those measured here, which might have an effect on recovery of the gut from infection and damage. In mice, treatment with cortisone acetate induces the maturation of enterocytes making them resistant to rotavirus infection (Wolf et al, 1981 ). This did not appear to be occurring in this study as rotavirus-naive DX-treated calves excreted similar levels of rotavirus as the DX-untreated animals.…”

I, 5. Treatment of viral gastroenteritis

“…Despite improvement in functional assays of the infected epithelium, epidermal growth factor and TGF failed to decrease diarrhea or increase weight gain in infected swine (Zijlstra, 1994;Rhoads et al, 1995). Corticosteroids lead to early maturation of the suckling mouse gut and prevented symptomatic murine rotavirus (EDIM) infection (Wolf et al, 1981). Corticosteroid treatment of suckling pigs infected with transmissable gastroenteritis virus lead to improved villous structure and improved sodium transport in intestinal mucosa (Rhoads et al, 1988).…”