Novel adenoviruses in wild primates: a high level of genetic diversity and evidence of zoonotic transmissions

Abstract

Adenoviruses (AdVs) broadly infect vertebrate hosts, including a variety of nonhuman primates (NHPs). In the present study, we identified AdVs in NHPs living in their natural habitats, and through the combination of phylogenetic analyses and information on the habitats and epidemiological settings, we detected possible horizontal transmission events between NHPs and humans. Wild NHPs were analyzed with a pan-primate AdV-specific PCR using a degenerate nested primer set that targets the highly conserved adenovirus DNA polymerase gene. A plethora of novel AdV sequences were identified, representing at least 45 distinct AdVs. From the AdV-positive individuals, 29 nearly complete hexon genes were amplified and, based on phylogenetic analysis, tentatively allocated to all known human AdV species (Human adenovirus A to Human adenovirus G [HAdV-A to -G]) as well as to the only simian AdV species (Simian adenovirus A [SAdV-A]). Interestingly, five of the AdVs detected in great apes grouped into the HAdV-A, HAdV-D, HAdV-F, or SAdV-A clade. Furthermore, we report the first detection of AdVs in New World monkeys, clustering at the base of the primate AdV evolutionary tree. Most notably, six chimpanzee AdVs of species HAdV-A to HAdV-F revealed a remarkably close relationship to human AdVs, possibly indicating recent interspecies transmission events.

Fig. 1.

DPOL sequence-based phylogenetic analysis. Partial DPOL gene sequences from the novel AdVs and from published NHP AdVs and human AdVs were aligned and subjected to phylogenetic analysis. The tree was reconstructed using maximum likelihood with the HKY85 model of substitutions, as described in Materials and Methods. AdVs from wild and captive NHPs discovered in this study are marked with red and black dots, respectively. All other NHP AdVs were reported previously and originated from captive animals. The branches of all AdVs that could tentatively be allocated to one of the species Human adenovirus A to G or to the species Simian adenovirus A are colored separately. Branches left without extra coloring belong to AdVs for which allocation to an AdV species was not possible. Bootstrap values are depicted at the nodes of the tree; nonsignificant values or those close to branch tips were omitted. AdV species and host compositions are indicated on the right. Numbers of AdVs found in each host species are given in parentheses: numbers of published AdVs are given before the slash, in black, and numbers of novel AdVs from this study are given behind the slash, in blue.

Fig. 2.

Phylogenetic analysis of the hexon gene. The hexon gene sequences of the novel AdVs and of published NHP AdVs and human HAdVs were aligned and subjected to phylogenetic analysis. The tree was reconstructed using maximum likelihood with the GTR+I+G model of substitutions, as described in Materials and Methods. Human, chimpanzee, bonobo, and gorilla AdVs are depicted in black, red, green, and blue, respectively. AdVs from wild and captive NHPs discovered in this study are marked with red and black dots, respectively. All other NHP AdVs were reported previously and originated from captive animals. The branches of all AdVs that could be allocated to one of the species Human adenovirus A to G or to the species Simian adenovirus A are colored separately. Branches left without extra coloring belong to AdVs for which tentative allocation to an AdV species was not possible. Bootstrap values are depicted at the nodes of the tree; nonsignificant values or those close to branch tips were omitted.