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Nat Microbiol. 2019 Sep 16. doi: 10.1038/s41564-019-0556-9. [Epub ahead of print]
Bat influenza viruses transmit among bats but are poorly adapted to non-bat species.
Ciminski K1,2, Ran W1,2, Gorka M3, Lee J4, Malmlov A5, Schink?the J6, Eckley M5, Murrieta RA5, Aboellail TA5, Campbell CL5, Ebel GD5, Ma J4, Pohlmann A3, Franzke K7, Ulrich R6, Hoffmann D3, Garc?a-Sastre A8,9,10, Ma W11, Schountz T12, Beer M13, Schwemmle M14,15.
Author information
1 Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany. 2 Faculty of Medicine, University of Freiburg, Freiburg, Germany. 3 Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Germany. 4 Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. 5 Arthropod Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. 6 Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald, Germany. 7 Institute of Infectology, Friedrich-Loeffler-Institut, Greifswald, Germany. 8 Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 10 Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 11 Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. wma@vet.k-state.edu. 12 Arthropod Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. Tony.Schountz@colostate.edu. 13 Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Germany. Martin.Beer@fli.de. 14 Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany. martin.schwemmle@uniklinik-freiburg.de. 15 Faculty of Medicine, University of Freiburg, Freiburg, Germany. martin.schwemmle@uniklinik-freiburg.de.
Abstract
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.
PMID: 31527796 DOI: 10.1038/s41564-019-0556-9
Bat influenza viruses transmit among bats but are poorly adapted to non-bat species.
Ciminski K1,2, Ran W1,2, Gorka M3, Lee J4, Malmlov A5, Schink?the J6, Eckley M5, Murrieta RA5, Aboellail TA5, Campbell CL5, Ebel GD5, Ma J4, Pohlmann A3, Franzke K7, Ulrich R6, Hoffmann D3, Garc?a-Sastre A8,9,10, Ma W11, Schountz T12, Beer M13, Schwemmle M14,15.
Author information
1 Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany. 2 Faculty of Medicine, University of Freiburg, Freiburg, Germany. 3 Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Germany. 4 Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. 5 Arthropod Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. 6 Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald, Germany. 7 Institute of Infectology, Friedrich-Loeffler-Institut, Greifswald, Germany. 8 Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 10 Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 11 Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. wma@vet.k-state.edu. 12 Arthropod Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. Tony.Schountz@colostate.edu. 13 Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Germany. Martin.Beer@fli.de. 14 Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany. martin.schwemmle@uniklinik-freiburg.de. 15 Faculty of Medicine, University of Freiburg, Freiburg, Germany. martin.schwemmle@uniklinik-freiburg.de.
Abstract
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.
PMID: 31527796 DOI: 10.1038/s41564-019-0556-9