Expected and Unexpected Features of the Newly Discovered Bat Influenza A-like Viruses

Ma, Wenjun; García-Sastre, Adolfo; Schwemmle, Martin

Recently, we succeeded in generating chimeric bat viruses in mammalian cells containing six internal genes from either influenza A-like HL17NL10 or HL18NL11 virus, with the remaining two surface genes encoding the HA and NA from a conventional IAV such as A/PR/ 8/1934 (H1N1), A/swine/Texas/4199-2/1998 (H3N2), or A/SC35M (H7N7) [8, 9] . To rescue these bat chimeras, it was essential to flank the canonical IAV HA and NA coding regions with the noncoding regions and part of the coding regions from the bat influenza A-like HA (HL17 or HL18) and NA (NL10 or NL11) segments, indicating RNA packaging incompatibilities between bat influenza A-like virus and conventional IAV segments (Fig 2) . The major packaging sequences of conventional IAV are located within these regions [14, 15] and vary only slightly, thereby allowing reassortment of viral genomes between different IAVs [16] . For efficient growth of bat chimeric viruses in mammalian cells or mice, adaptive mutations are not necessarily required. However, viral replication and pathogenicity in mice is dependent to a certain degree on the HA/NA combination used [8] . The HL17NL10-based bat chimeric virus with the viral surface glycoproteins of a mouse adapted H7N7 virus (A/SC35M) shows limited replication and no pathogenicity in mice [9] , while mice infected with a comparable virus dose of the chimera with HA and NA coding regions from A/PR8/H1N1 died from extensive lung pathology, typically observed with conventional IAV [8] . Whether this is due to an intrinsic feature of the different HA/NAs or the interplay between viral surface glycoproteins and internal genes of the bat influenza A-like viruses remains to be determined.