SummaryA nonlethal influenza infection [A/PC/1/73 (H3Nz)l was given to infant mice to determine (1) the pathology of tracheal epithelium and lung, (2) the time course of viral shedding from the nose and lung, and (3) the subsequent development of protective immunity during adulthood.Both desquamation of the tracheal epithelium and lung pathology similar to that described in adults after influenza infection were observed in the infant. Animals infected at 3 days of age show virus shedding in 12 of 13 infant mice that persists for at least 2 days longer than in the adult. This longer duration of influenza infection did not result from either malnutrition or from intralitter transmission of virus. Recovery from virus shedding in both the upper and lower airway occurred in the absence of detectable serum antibody in six of seven mice. Infants that recover from infection, when rechallenged during adulthood, manifest complete protection in 11 of 13 mice after nonlethal challenge and no mortality after lethal challenge. Abbreviations EID50, egg infectious dose 50% MID50, mouse infectious dose 50% MLD5,, mouse lethal dose 50% NK, natural killer Influenza infection is responsible for producing significant morbidity and mortality in the human infant (4,14). The pathology of influenza disease in the adult mouse corresponds to influenza in human adults (22). This suggests that the young mouse might be a good model for studying factors responsible for the severity of influenza in the infant human. Although studies of lethal influenza infection of infant animals have been reported (3,5,12,19,23), the suitability of the infant mouse as a model for nonlethal influenza infection in the newborn has not been reported. We therefore undertook the present study to determine (1) the pathology of influenza infection, (2) recovery from influenza virus shedding, and (3) the development of subsequent protective immunity against influenza in the infant mouse.
MATERIALS AND METHODS
Animals.Eight to ten-week-old, inbred Swiss white mice of the A/J strain were obtained from Jackson Laboratories, Bar Harbor, ME. These animals were housed and bred in the animal facilities of the College of Medicine, University of Florida. All experimental and control mice were housed in the same environment and treated similarly.Breeding. Eight female mice were housed per cage and separated from male mice for at least 1 wk before breeding. At the time of mating no more than two female mice were placed in each cage containing one male. Males were removed at the end of 4 days. Two weeks later, pregnant females were isolated in individual cages. Approximately 20% of mothers would deliver on each of 2 days, 21 days after the 4-day breeding period.Virus. A/Port Chalmers/l/73 (A/PC/1/73 H3N2) influenza virus was originally obtained from the Research Resources Branch, National Institutes of Allergy and Infectious Disease. This was passaged multiple times in eggs to provide a large stock of virus that contained EID50/ml. This virus was also passaged six times in mouse ...