Evolution and Cryo-electron Microscopy Capsid Structure of a North American Bat Adenovirus and Its Relationship to Other Mastadenoviruses

Abstract

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.IMPORTANCE 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.

The Role of Hexon Protein as a Molecular Mold in Patterning the Protein IX Organization in Human Adenoviruses

“…1). Consistent with the previous observations [9–11], we suggest that the presence or absence of a (~20 aa) stretch of Ala and Ser residues in the linker region appears to determine whether or not the C-termini of IX molecules form the characteristic tetrameric coiled-coils seen in HAdVs or trimeric coiled-coils in non-HAdVs. The structural superposition of the conserved NTT regions of four unique IX molecules in HAdVs revealed two locations (S61 and S94) at which the linker region bends at an angle of 120°, in congruence with the corners of the hexagonal-shaped base of the hexon subunits (Fig 1d).…”

“…Of note, IX is uniquely present (conserved) in primate adenoviruses that belong to the genus Mastadenovirus in the family Adenoviridae [8]. While the N-terminal triskelion-forming region of IX (NTT; residues 1–62 in HAdV-D26) and the C-terminal coiled-coil forming region (CTC; residues 95–134 in HAdV-D26) are highly conserved, the length and composition of the linker region connecting the two signature structural elements of IX differs between the human and nonhuman AdVs (non-HAdVs) [9–11] (Supplementary Fig. 1).…”

Viral Diversity of Microbats within the South West Botanical Province of Western Australia

“…However, we detected an identical single adenovirus strain from N. geffroyi and N. gouldi collected at two separate regions. The small amplicon used for phylogenetic analysis may fail to discern a taxonomic separation between these two closely related species, although previous studies have reported the occurrence of divergent and cosmopolitan AdV strains [57,74,75]. However, evidence supporting this hypothesis has been based on a small amplicon and further studies on the co-evolution of adenoviruses and bats will benefit from whole genome analysis.…”

Two novel adenoviruses found in Cave Myotis bats (Myotis velifer) in Oklahoma

“…Little work has been done to investigate AdVs in North American species of bats; however, these studies [19,29] and ours highlight the importance of identifying viruses housed in bats to better understand viral evolution, how viruses are maintained in bat colonies and evaluate risks for host transmission to other species. Li et al [8] found their novel bat AdV (BtAdV-TJM) was capable of infecting several mammalian cells from different species, including humans, which indicates that bat AdVs possibly have a wide host range.…”

“…Since bats are known reservoirs of numerous viruses and cross-species transmission has been documented for an AdV, it will be useful to know which AdVs bats carry. AdV strains have been found in more than 45 species of bats across their global distribution [6,8,12,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] with seven species proposed by the International Committee on Taxonomy of Viruses [35]. These studies represent a start at investigating bat AdVs, but there is a need for additional studies considering there are over 1300 species of bats [2] and few North American bats have been investigated.…”