Co-circulation of influenza A virus strains and emergence of pandemic via reassortment: the role of cross-immunity.

Reassortment is an important evolutionary route for influenza A viruses to generate pandemic strains. The pre-requisite for reassortment to occur is co-infection of different influenza virus strains in the same host population. Empirical evidence suggests that co-circulation of influenza A virus strains is common and co-infection in patients has been reported. Whether a novel virus can successfully spread among a host population is determined by its life-history (infectivity and infectious period). It is also well known that different influenza A strains interfere through the immune response of human body cells. The reassortant virus strain generated from co-infections deviates dramatically in antigenic and genetic properties from its parental strains such that human populations have limited immunity against it. We consider a mathematical model which includes two strains of influenza virus within a standard SIR model and integrate life history and cross-immunity into the evolutionary dynamics of influenza virus. We assume that, following primary infection by one strain and recovery, individuals are susceptible to secondary infection by the other strain only but with reduced probability due to cross-immunity. Co-infection is included to examine how life-history and cross-immunity interplay to regulate the co-circulation and co-infection of different influenza A virus strains in human populations. Further, we introduce novel strains via reassortment and investigate how the opportunities of a reassortant strain developing into a pandemic are constrained by its life-history and the residual immunity within human populations. We find that though the probability of pandemic emergence via reassortment increases with transmissibility of reassortant strains and the rate of reassortment, the existence of cross-immunity acquired through previous infections or vaccination can greatly constrain pandemic emergence.
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