Are pigs overestimated as a source of zoonotic influenza viruses?

Abstract

Background: Swine influenza caused by influenza A viruses (IAV) directly affects respiratory health and indirectly impairs reproduction rates in pigs causing production losses. In Europe, and elsewhere, production systems have intensified featuring fewer holdings but, in turn, increased breeding herd and litter sizes. This seems to foster swine IAV (swIAV) infections with respect to the entrenchment within and spread between holdings. Disease management of swine influenza is difficult and relies on biosecurity and vaccination measures. Recently discovered and widely proliferating forms of self-sustaining modes of swIAV infections in large swine holdings challenge these preventive concepts by generating vaccine-escape mutants in rolling circles of infection.

Main body: The most recent human IAV pandemic of 2009 rooted at least partly in IAV of porcine origin highlighting the zoonotic potential of swIAV. Pigs constitute a mixing vessel of IAV from different species including avian and human hosts. However, other host species such as turkey and quail but also humans themselves may also act in this way; thus, pigs are not essentially required for the generation of IAV reassortants with a multispecies origin. Since 1918, all human pandemic influenza viruses except the H2N2 virus of 1958 have been transmitted in a reverse zoonotic mode from human into swine populations. Swine populations act as long-term reservoirs of these viruses. Human-derived IAV constitute a major driver of swIAV epidemiology in pigs. Swine-to-human IAV transmissions occurred rarely and mainly sporadically as compared to avian-to-human spill-over events of avian IAV. Yet, new swIAV variants that harbor zoonotic components continue to be detected. This increases the risk that such components might eventually reassort into viruses with pandemic potential.

Conclusions: Domestic pig populations should not be globally stigmatized as the only or most important reservoir of potentially zoonotic IAV. The likely emergence from swine of the most recent human IAV pandemic in 2009, however, emphasized the principal risks of swine populations in which IAV circulate unimpededly. Implementation of regular and close-meshed IAV surveillance of domestic swine populations to follow the dynamics of swIAV evolution is clearly demanded. Improved algorithms for directly inferring zoonotic potential from whole IAV genome sequences as well as improved vaccines are still being sought.

Keywords: Mixing vessel; Reverse zoonosis; Surveillance; Swine influenza A virus; Zoonotic potential.

Fig. 1

Schematic presentation of putative “mixing vessel” host species (pigs, quails, turkeys, humans) which express sialic acid receptors for both avian- and human-adapted influenza A viruses (IAV) in their respiratory tracts. Hence, they are considered susceptible for a wider range of IAV of different host origins. Co-infections with different IAV create reassortment opportunities increasing the likelihood of the formation of reassortants with increased zoonotic or pre-pandemic propensity

Fig. 2

Proposed scheme of mutual transmissions of influenza A viruses (IAV) between human and porcine populations. Reverse zoonotic IAV transmission from humans to swine is a major driver of IAV diversity in pigs. “Historic” human IAV lineages may circulate for prolonged periods in pigs when their counterparts in humans have already been replaced; co-infections of such viruses in pigs with other IAV of porcine or avian origin may produce reassortants with enhanced zoonotic or even pre-pandemic potential. Zoonotic transmission back to the adult human population is probably sporadic and rare due to their substantial cross-reactive immunity (red barrier). Children and immunocompromised patients, in contrast, may have a higher susceptibility