Possible reason for cross-species and cross-subtype reassortment in polymerase basic protein 2 from influenza A virus

The reassortment in proteins from influenza A viruses among human, swine, and Eurasian avian strains formed a new influenza A virus leading to the first pandemic in this century, which suggests that the barrier between species and between subtypes would not be strong enough to prevent the cross-species infection and cross-subtype reassortment from occurring. In this study, we intensively used the ANOVA including its model I and model II to analyze 2430 polymerase basic proteins 2 (PB2) of influenza A viruses in order to determine whether there is a barrier between species and between subtypes. The results show that (i) there is a barrier between HA subtypes, between NA subtypes and between hosting species in some cases, however, there is no barrier in most cases, which can lead to cross-species infection and cross-subtype reassortment, and (ii) the intra-subtype/species variation is larger than the inter-subtype/species variation in most cases, which can lead mutations/reassortments in PB2 to easily jump from species to species or from subtype to subtype. These results are in agreement with our previous studies along this research line in the hemagglutinin, neuraminidase, matrix protein 1 and 2 from influenza A virus, and provide further explanations for the possible reason for cross-subtype reassortment and cross-species infection.