A Zoonotic Adenoviral Human Pathogen Emerged through Genomic Recombination among Human and Nonhuman Simian Hosts

Abstract

Genomics analysis of a historically intriguing and predicted emergent human adenovirus (HAdV) pathogen, which caused pneumonia and death, provides insight into a novel molecular evolution pathway involving “ping-pong” zoonosis and anthroponosis. The genome of this promiscuous pathogen is embedded with evidence of unprecedented multiple, multidirectional, stable, and reciprocal cross-species infections of hosts from three species (human, chimpanzee, and bonobo). This recombinant genome, typed as HAdV-B76, is identical to two recently reported simian AdV (SAdV) genomes isolated from chimpanzees and bonobos. Additionally, the presence of a critical adenoviral replication element found in HAdV genomes, in addition to genes that are highly similar to counterparts in other HAdVs, reinforces its potential as a human pathogen. Reservoirs in nonhuman hosts may explain periods of apparent absence and then reemergence of human adenoviral pathogens, as well as present pathways for the genesis of those thought to be newly emergent. The nature of the HAdV-D76 genome has implications for the use of SAdVs as gene delivery vectors in human gene therapy and vaccines, selected to avoid preexisting and potentially fatal host immune responses to HAdV. IMPORTANCE An emergent adenoviral human pathogen, HAdV-B76, associated with a fatality in 1965, shows a remarkable degree of genome identity with two recently isolated simian adenoviruses that contain cross-species genome recombination events from three hosts: human, chimpanzee, and bonobo. Zoonosis (nonhuman-to-human transmission) and anthroponosis (human to nonhuman transmission) may play significant roles in the emergence of human adenoviral pathogens.

Genomics‐based re‐examination of the taxonomy and phylogeny of human and simian Mastadenoviruses: an evolving whole genomes approach, revealing putative zoonosis, anthroponosis, and amphizoonosis

“…A third, archived genome from 1967, has been recently sequenced and reported to show near identity to the above two genomes as well (manuscript in preparation). As it was isolated from a human host and led to a respiratory illness and fatality, it has been renamed HAdV-76 (Dehghan et al, 2019), rather than "SAdV-35.3" or the original designation "21 + 16/16". These three genomes contain recombination events from SAdV-21 (chimpanzee), HAdV-21 (human), SAdV-27 (chimpanzee), and HAdV-16 (human) (Dehghan et al, 2013a;Dehghan et al, 2019).…”

“…As it was isolated from a human host and led to a respiratory illness and fatality, it has been renamed HAdV-76 (Dehghan et al, 2019), rather than "SAdV-35.3" or the original designation "21 + 16/16". These three genomes contain recombination events from SAdV-21 (chimpanzee), HAdV-21 (human), SAdV-27 (chimpanzee), and HAdV-16 (human) (Dehghan et al, 2013a;Dehghan et al, 2019). This striking example underscores why AdVs may be one of the few, if not the only, model organisms to explore and understand the phenomenon of "amphizoonosis", that is, cross-species transmissions occurring in both directions.…”

“…Sequence recombination within the separate groups of HAdV and SAdV genomes has been reported as an important mechanism of adenovirus evolution, leading to novel and emergent viruses and pathogens (Walsh et al, 2009;Walsh et al, 2010;Robinson et al, 2011;Robinson et al, 2013;Hoppe et al, 2015b). Surprisingly, genome recombination between HAdVs and SAdVs has also been reported, suggesting zoonosis and anthroponosis (Dehghan et al, 2013a;Dehghan et al, 2019), along with complementing reports of cross-species viral transmissions between humans and other simians that elicited neutralizing antibodies in both (Xiang et al, 2006;Roy et al, 2009;Ersching et al, 2010;Wevers et al, 2011;Chen et al, 2011b;Chiu et al, 2013;Pauly et al, 2015;Hoppe et al, 2015a). To provide a high-resolution and more comprehensive view of the phylogenetic relationships and taxonomy of HAdVs and SAdVs, this report uses a broader examination of all published HAdV and SAdV genomes to yield heuristically parsimonious phylogenomic trees.…”

Seroprevalence of Neutralizing Antibodies against Six Human Adenovirus Types Indicates the Low Level of Herd Immunity in Young Children from Guangzhou, China

“…Human adenoviruses (HAdVs) are non-enveloped, double-stranded DNA viruses and are divided into seven species (A–G). To date, approximately 100 types have been recognized according to genomic sequences ( https://hadvwg.gmu.edu/ ) (Seto et al 2011 ; Dehghan et al 2019 ). HAdVs are highly contagious pathogens that exhibit a variety of tissue tropisms, and cause many diseases, such as acute respiratory disease (ARD), gastroenteritis, cystitis, keratoconjunctivitis, carditis, meningoencephalitis, depending on the infection type.…”

Genomic foundations of evolution and ocular pathogenesis in human adenovirus species D

“…Since both HAdV‐B21 and ‐B16 are human respiratory pathogens, it was suggested that SAdV‐B35 could be a nascent human respiratory pathogen. This idea proved prescient when a recent analysis of an adenovirus originally isolated from a fatal respiratory infection in a 6‐year‐old boy in 1965 revealed a virus genome nearly identical to SAdV‐B35 . This interspecies recombinant was typed as HAdV‐B76.…”