The time-interval between infections and viral hierarchies are determinants of viral interference following influenza virus infection in a ferret model (#23)
Epidemiological studies suggest that following infection with influenza virus, there is a short period of time during which the host experiences a lower susceptibility to infection with other influenza viruses. This viral interference, also termed ‘a temporary state of immunity’, appears to be independent of the antigenic similarities between the two viruses. In this study, we used the ferret model of human influenza to systematically investigate viral interference and the role it plays in determining the outcome of consecutive infections. Ferrets were first infected then challenged 1 to 14 days later with pairs of influenza A(H1N1)pdm09 and influenza B viruses that were circulating in humans in 2009 and 2010. Challenge outcomes varied depending on the virus combination and time-interval between primary infection and challenge. Infection with A(H1N1)pdm09 virus was observed to prevent or delay infection with an influenza B virus. Infection with an influenza B virus delayed the subsequent infection with A(H1N1)pdm09 viruses. Co-infections occurred when short periods (1 or 3 day intervals) separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Overall, these data indicate that both the time-interval between infections and the sequential combination of viruses presented are important determinants of the degree of viral interference. Influenza viruses appear to have an ordered hierarchy according to their ability to block/delay infection, which may contribute to the dominance of different viruses often seen in an influenza season. Exploiting mechanisms that induce this temporary immunity may provide novel vaccine or therapeutic strategies to overcome influenza and other respiratory diseases.