Host adaptation and transmission of influenza A viruses in mammals

Abstract

A wide range of influenza A viruses of pigs and birds have infected humans in the last decade, sometimes with severe clinical consequences. Each of these so-called zoonotic infections provides an opportunity for virus adaptation to the new host. Fortunately, most of these human infections do not yield viruses with the ability of sustained human-to-human transmission. However, animal influenza viruses have acquired the ability of sustained transmission between humans to cause pandemics on rare occasions in the past, and therefore, influenza virus zoonoses continue to represent threats to public health. Numerous recent studies have shed new light on the mechanisms of adaptation and transmission of avian and swine influenza A viruses in mammals. In particular, several studies provided insights into the genetic and phenotypic traits of influenza A viruses that may determine airborne transmission. Here, we summarize recent studies on molecular determinants of virulence and adaptation of animal influenza A virus and discuss the phenotypic traits associated with airborne transmission of newly emerging influenza A viruses. Increased understanding of the determinants and mechanisms of virulence and transmission may aid in assessing the risks posed by animal influenza viruses to human health, and preparedness for such risks.

Keywords: adaptation; influenza A virus; transmission; virulence.

Figure 1

Traits important for airborne transmission of influenza virus between mammals. Increased binding of HA to appropriate cells of the URT of mammalian host cells contributes to the airborne transmissibility. Increased acid stability of the HA was also observed in airborne transmissible virus. Adaptation of the polymerase complex is necessary to facilitate increased replication in the mammalian host cell and is a likely determinant of airborne transmissibility. Although this has not (yet) been shown directly, the release of single viral particles instead of aggregates may aid the airborne transmissibility of the virus, which may be regulated by the HA–NA balance. Virus attachment and budding images were described previously. Fusion and replication data are unpublished. The fusion picture is hypothetical and shows a non-adapted HA with a high pH threshold for fusion and an adapted HA with a decreased pH threshold for fusion. The replication figure contains data of the Indonesia/5/05 polymerase complex and Indonesia/5/05 airborne transmissible polymerase complex by Herfst et al.