Multiple Cross-Species Transmission Events of Human Adenoviruses (HAdV) during Hominine Evolution

Abstract

Human adenoviruses (HAdV; species HAdV-A to -G) are highly prevalent in the human population, and represent an important cause of morbidity and, to a lesser extent, mortality. Recent studies have identified close relatives of these viruses in African great apes, suggesting that some HAdV may be of zoonotic origin. We analyzed more than 800 fecal samples from wild African great apes and humans to further investigate the evolutionary history and zoonotic potential of hominine HAdV. HAdV-B and -E were frequently detected in wild gorillas (55%) and chimpanzees (25%), respectively. Bayesian ancestral host reconstruction under discrete diffusion models supported a gorilla and chimpanzee origin for these viral species. Host switches were relatively rare along HAdV evolution, with about ten events recorded in 4.5 My. Despite presumably rare direct contact between sympatric populations of the two species, transmission events from gorillas to chimpanzees were observed, suggesting that habitat and dietary overlap may lead to fecal-oral cross-hominine transmission of HAdV. Finally, we determined that two independent HAdV-B transmission events to humans occurred more than 100,000 years ago. We conclude that HAdV-B circulating in humans are of zoonotic origin and have probably affected global human health for most of our species lifetime.

Phylogenomic evidence for recombination of adenoviruses in wild gorillas

“…In a previous study, faecal samples had been collected from w300 wild gorillas, free-ranging in six locations of sub-Saharan Africa. Of these, 55 % had tested PCR positive for sequences attributable to HAdV-B (Hoppe et al, 2015). In the present study, seven samples were selected for genome-wide analysis that apparently had the highest HAdV-B loads.…”

“…HAdV-B subclades were named with the abbreviation H (for human AdV) and A (ape AdV) and consecutively numbered (H1-H3; A1-A3). Since the pVII-pVI gene region of AdVs is a recombination cold spot (Hoppe et al, 2015) and the HAdV-B clade in the pVII-pVI tree was the least expanded and also best supported in its deeper branches, the six subclades (H1-H3; A1-A3) in the tree's HAdV-B clade (Fig. 1b) were assigned as reference subclades for the assessment of the subclades in the penton base, hexon and fiber gene-based trees (Fig.…”

“…We therefore investigated whether AdV recombination occurs in great apes living in the wild. Previously, we co-amplified different AdV types of species HAdV-B from the same gorilla samples by PCR, this being indicative for HAdV-B coinfection in wild gorillas and an obvious prerequisite for HAdV-B recombination (Hoppe et al, 2015). To search for signs of recombination events we performed in the present study a comparative phylogenomic approach and analysed general hot spots of AdV recombination, i.e.…”

“…AdVs attributable to nearly all HAdV species have been detected in wild and captive African great apes and are shed with faeces in high numbers (Duncan et al, 2013;Hoppe et al, 2015;Roy et al, 2009;Seimon et al, 2015;Wevers et al, 2010Wevers et al, , 2011. In captive NHPs, AdVs are associated with respiratory disease (Chen et al, 2011;Chiu et al, 2013;Wevers et al, 2010), but almost nothing is known about the clinical relevance of AdVs in wild NHP populations.…”

“…In captive NHPs, AdVs are associated with respiratory disease (Chen et al, 2011;Chiu et al, 2013;Wevers et al, 2010), but almost nothing is known about the clinical relevance of AdVs in wild NHP populations. AdVs have been reported to be transmitted between primate species, including zoonotic transmission to humans (Chen et al, 2011;Chiu et al, 2013;Ersching et al, 2010;Hoppe et al, 2015;Lonsdorf et al, 2014;Mwenda et al, 2005;Xiang et al, 2006), demonstrating their ability to switch between primate hosts.…”