Evolution and Cryo-electron Microscopy Capsid Structure of a North American Bat Adenovirus and Its Relationship to Other Mastadenoviruses.
Since the first description of adenoviruses in bats in 2006, a number of micro- and megabat species in Europe, Africa, and Asia have been shown to carry a wide diversity of adenoviruses. Here, we report on the evolutionary, biological, and structural characterization of a novel bat adenovirus (BtAdV) recovered from a Rafinesque's big-eared bat (Corynorhinus rafinesquii) in Kentucky, USA, which is the first adenovirus isolated from North American bats. This virus (BtAdV 250-A) exhibits a close phylogenetic relationship with Canine mastadenovirus A (CAdV A), as previously observed with other BtAdVs. To further investigate the relationships between BtAdVs and CAdVs, we conducted mass spectrometric analysis and single-particle cryo-electron microscopy reconstructions of the BtAdV 250-A capsid and also analyzed the in vitro host ranges of both viruses. Our results demonstrate that BtAdV 250-A represents a new mastadenovirus species that, in contrast to CAdV, has a unique capsid morphology that contains more prominent extensions of protein IX and can replicate efficiently in a phylogenetically diverse range of species. These findings, in addition to the recognition that both the genetic diversity of BtAdVs and the number of different bat species from disparate geographic regions infected with BtAdVs appears to be extensive, tentatively suggest that bats may have served as a potential reservoir for the cross-species transfer of adenoviruses to other hosts, as theorized for CAdV.


OBJECTIVE
Although many adenoviruses are host specific and likely codiverged with their hosts over millions of years, other adenoviruses appear to have emerged through successful cross-species transmission events on more recent time scales. The wide geographic distribution and genetic diversity of adenoviruses in bats and their close phylogenetic relationship to Canine mastadenovirus A (CAdV A) has raised important questions about how CAdV A, and possibly other mammalian adenoviruses, may have emerged. Although most adenoviruses tend to cause limited disease in their natural hosts, CAdV A is unusual in that it may cause high morbidity and sometimes fatal infections in immunocompetent hosts and is thus an important pathogen of carnivores. Here, we performed a comparative evolutionary and structural study of representative bat and canine adenoviruses to better understand the relationship between these two viral groups.
Department of Medicine, The Pennsylvania State College of Medicine, Hershey, Pennsylvania, USA.
Nicole
N
Hackenbrack
Department of Computational and Systems Biology, Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Matthew B
MB
Rogers
Department of Medicine, The Pennsylvania State College of Medicine, Hershey, Pennsylvania, USA.
Robert E
RE
Ashley
Southeastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
M Kevin
MK
Keel
Southeastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
Steven V
SV
Kubiski
Southeastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
John A
JA
Bryan
Department of Computational and Systems Biology, Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Elodie
E
Ghedin
Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Edward C
EC
Holmes
Department of Medicine, The Pennsylvania State College of Medicine, Hershey, Pennsylvania, USA.
Susan L
SL
Hafenstein
Southeastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA aba25@vt.edu.|Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.|Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, USA.
Andrew B
http://orcid.org/0000-0003-0971-1215
AB
Allison
D000257:Adenoviridae Infections / Q000635:transmission* / Q000821:virology*; D000818:Animals; D005075:Biological Evolution; D002213:Capsid / Q000378:metabolism* / Q000648:ultrastructure*; D002685:Chiroptera; D020285:Cryoelectron Microscopy; D004285:Dogs; D023061:Gene Order; D016679:Genome, Viral; D058507:Host Specificity; D013058:Mass Spectrometry; D017921:Mastadenovirus / Q000145:classification / Q000502:physiology* / Q000648:ultrastructure*; D016366:Open Reading Frames; D010802:Phylogeny; D012367:RNA, Viral; D017385:Sequence Homology; D014771:Virion
D012367:RNA, Viral
bat adenovirus; canine adenovirus; cross-species transmission; cryo-electron microscopy; host range; mastadenovirus; virus evolution