Interaction of Nippostrongylus brasiliensis and Influenza Virus in Mice. I. Influence of the Nematode on the Virus

The effects of Nippostrongylus brasiliensis and Nematospiroides dubius upon the pathogenicity of influenza virus (A2/Japan/170/62E3M14E1MMEi) in mice were studied in a series of experiments. Two patterns of exposure to larvae and virus were used. In one mice were exposed to nematode larvae and virus on the same day, while in the other mice were exposed to nematode larvae 2 weeks prior to exposure to virus. Mortalities during the first 10 days after exposure to virus were noted, and on the 10th day all surviving mice were killed and examined for lung consolidation. The number of deaths and lung consolidation that occurred in mice which were exposed to N. brasiliensis larvae and virus on the same day was significantly greater than that which occurred when mice were exposed only to virus. This enhancing effect was not observed in the experiments in which N. dubius was used or in experiments in which N. brasiliensis larvae were administered 2 weeks before virus. The results were interpreted to indicate that the presence of migrating N. brasiliensis larvae in the lungs of the mice at the time of virus multiplication was principally responsible for the enhancing effects observed. In attempting to develop a model system to study helminths as vectors of animal viruses several groups of mice were infected concurrently with the nematode Nippostrongylus brasiliensis (Travassos, 1914) and influenza virus. A higher percentage of mortality was observed in some of these groups of mice than in groups of mice infected only with the nematode or only with the virus. Other investigators (Jarrett et al., 1953; Mackenzie, 1963; Nayak et al., 1964; Nayak and Kelley, 1965; Underdahl and Kelley, 1957; Underdahl, 1958) have reported similar findings in studying the influence of helminths on respiratory infections in animals, but the present observations were unique when first described (Wescott and Todd, 1964) in that the additive effect observed was apparently influenced by the time of exposure to the virus in relation to the time of exposure to the nematode. Our interest in the interaction we observed was that it might have an effect or be used Received for publication 20 October 1965. * From the Department of Veterinary Science, University of Wisconsin, Madison, Paper NS 497. This investigation was supported in part by a Public Health Service Fellowship (EPD15,937) from the NIAID, Public Health Service, in part by the American Cancer Society Institutional Research Grant to the University of Wisconsin, and in part by a Public Health Service Research Grant (Al 06452-01). t Present address: School of Veterinary Medicine, University of Missouri, Columbia, Missouri. to advantage in subsequent experiments dealing with the transmission of influenza virus by N. brasiliensis. For these reasons, the studies reported here were performed to enlarge upon our preliminary observations and to more fully determine the nature of the enhancing effect of N. brasiliensis upon influenza virus infection in mice. Basically these studies were designed to investigate the role the lung migration of N. brasiliensis played in enhancement. The relationship of migrating larvae in the lungs of mice to the severity of the virus disease was determined in two ways. In one the effects of N. brasiliensis were compared to the effects produced by Nematospiroides dubius (Baylis, 1926), a nematode parasite somewhat similar to N. brasiliensis but without a lung migration. In the other N. brasiliensis larvae were allowed to complete their lung migration before mice were exposed to influenza virus and the results compared to those obtained when concurrent infection of the lungs with virus and larvae were produced. MATERIALS AND METHODS Experimental animals and exposures The animals used in these experiments were conventional ARS/ICR strain, random-bred, 4to 5week-old male mice, supplied by a local breeder (A. R. Schmidt Co., Madison, Wis.). A minimum of 84 mice were used in each experiment. The mice were divided into groups of six when received at this laboratory and kept in these groupings in