TY - JOUR
T1 - Bat influenza viruses transmit among bats but are poorly adapted to non-bat species
AU - Ciminski, Kevin
AU - Ran, Wei
AU - Gorka, Marco
AU - Lee, Jinhwa
AU - Malmlov, Ashley
AU - Schinköthe, Jan
AU - Eckley, Miles
AU - Murrieta, Reyes A.
AU - Aboellail, Tawfik A.
AU - Campbell, Corey L.
AU - Ebel, Gregory D.
AU - Ma, Jingjiao
AU - Pohlmann, Anne
AU - Franzke, Kati
AU - Ulrich, Reiner
AU - Hoffmann, Donata
AU - García-Sastre, Adolfo
AU - Ma, Wenjun
AU - Schountz, Tony
AU - Beer, Martin
AU - Schwemmle, Martin
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Major histocompatibility complex class II (MHC-II) molecules of multiple species function as cell-entry receptors for the haemagglutinin-like H18 protein of the bat H18N11 influenza A virus, enabling tropism of the viruses in a potentially broad range of vertebrates. However, the function of the neuraminidase-like N11 protein is unknown because it is dispensable for viral infection or the release of H18-pseudotyped viruses. Here, we show that infection of mammalian cells with wild-type H18N11 leads to the emergence of mutant viruses that lack the N11 ectodomain and acquired mutations in H18. An infectious clone of one such mutant virus, designated rP11, appeared to be genetically stable in mice and replicated to higher titres in mice and cell culture compared with wild-type H18N11. In ferrets, rP11 antigen and RNA were detected at low levels in various tissues, including the tonsils, whereas the wild-type virus was not. In Neotropical Jamaican fruit bats, wild-type H18N11 was found in intestinal Peyer’s patches and was shed to high concentrations in rectal samples, resulting in viral transmission to naive contact bats. Notably, rP11 also replicated efficiently in bats; however, only restored full-length N11 viruses were transmissible. Our findings suggest that wild-type H18N11 replicates poorly in mice and ferrets and that N11 is a determinant for viral transmission in bats.
AB - Major histocompatibility complex class II (MHC-II) molecules of multiple species function as cell-entry receptors for the haemagglutinin-like H18 protein of the bat H18N11 influenza A virus, enabling tropism of the viruses in a potentially broad range of vertebrates. However, the function of the neuraminidase-like N11 protein is unknown because it is dispensable for viral infection or the release of H18-pseudotyped viruses. Here, we show that infection of mammalian cells with wild-type H18N11 leads to the emergence of mutant viruses that lack the N11 ectodomain and acquired mutations in H18. An infectious clone of one such mutant virus, designated rP11, appeared to be genetically stable in mice and replicated to higher titres in mice and cell culture compared with wild-type H18N11. In ferrets, rP11 antigen and RNA were detected at low levels in various tissues, including the tonsils, whereas the wild-type virus was not. In Neotropical Jamaican fruit bats, wild-type H18N11 was found in intestinal Peyer’s patches and was shed to high concentrations in rectal samples, resulting in viral transmission to naive contact bats. Notably, rP11 also replicated efficiently in bats; however, only restored full-length N11 viruses were transmissible. Our findings suggest that wild-type H18N11 replicates poorly in mice and ferrets and that N11 is a determinant for viral transmission in bats.
UR - http://www.scopus.com/inward/record.url?scp=85073823953&partnerID=8YFLogxK
U2 - 10.1038/s41564-019-0556-9
DO - 10.1038/s41564-019-0556-9
M3 - Article
C2 - 31527796
AN - SCOPUS:85073823953
SN - 2058-5276
VL - 4
SP - 2298
EP - 2309
JO - Nature Microbiology
JF - Nature Microbiology
IS - 12
ER -