Novel insights into bat influenza A viruses

Abstract

In 2012 and 2013, influenza virus genome sequences of two new influenza A virus (IAV) subtypes were discovered in bat specimens, but further characterization was largely impeded by the lack of infectious virus. With the identification of highly susceptible cell lines, reconstitution of infectious bat IAV by reverse genetics recently succeeded and allowed a first insight into the life cycle of these viruses. Although there is a certain degree of functional compatibility between bat and conventional influenza A virus proteins, there are striking differences, including receptor usage, polarity of infection and reassortment potential.

Keywords: bats; glycoproteins; influenza A viruses; packaging; reassortment; zoonosis.

Fig. 1.

Co-infection of cells with bat and conventional influenza A viruses does not result in reassortment events. (a) The exchange of genomic segments is known to take place in cells co-infected with different conventional IAV subtypes. Likewise, based on experiments with chimeric bat influenza viruses, genomic reassortment is believed to occur in cells co-infected with the known bat IAV subtypes. However, reassortment between conventional and bat IAVs is blocked, probably due to incompatibility of the vRNA packaging signals and NP. (b and c) Highly conserved amino acids located in either the head (grey) or body (black) domain of a conventional IAV NP of the H7N7 subtype (A/SC35M) were partially substituted with the corresponding amino acids present in the HL17NL10 NP (b). Bat-specific amino acids introduced in the head or body domain are highlighted in pink or yellow, respectively. H7N7 viruses encoding these NP mutants demonstrated a genome packaging deficiency (c). The incorporation of different RNA segment subsets into viral particles was differentially affected, depending on whether the mutations were introduced into the head or body domain. The relative ratio of genome subsets identified in viral particle preparations is shown (raw data from Moreira et al. [40]). Genome levels of wild-type (WT) H7N7 were set to 1. Column colours correspond to the amino acid substitutions in either the head or body domain.

Fig. 2.

Bat and conventional IAVs exhibit different entry mechanisms in polarized epithelial cells. Conventional IAVs initiate the infection at the apical site of epithelial cells by receptor-mediated endocytosis after the binding of HA to sialic acid containing oligosaccharides exposed on the host cell surface. Following completion of the IAV replication cycle, progeny virions are then released from the apical plasma membrane where NA facilitates the cleavage of sialic acid residues. In contrast, bat IAVs enter polarized epithelial cells preferentially from the basolateral site via endocytosis upon binding of HL to a yet unknown receptor. Budding of progeny bat IAV virions occurs similarly to conventional IAV at the apical plasma membrane.