Madagascar as a Hotspot for Viral Discovery: The Oral DNA Viromes of Lemurs and Rodents from Captive to Natural Populations

Abstract

Madagascar is a biodiversity hotspot characterized by both incredible endemism of animals (e.g., lemurs and Nesomyinae rodents) and intense anthropogenic pressures. The lemuriform primates are one of the most endangered and speciose primate lineages yet have remained remarkably understudied for viruses. We hypothesize that viruses in Malagasy animals, particularly DNA viruses known to co-evolve with their hosts, will be highly divergent, reflecting the geographic isolation and subsequently rich evolutionary history of mammals in Madagascar. Using viral metagenomic approaches, my dissertation aims to test this overarching hypothesis by: (1) building foundational knowledge of viral communities in captive lemur populations and human caretakers, and (2) characterizing lemur, endemic rodent, and nonnative rodent oral DNA viral diversity in natural populations in southeastern Madagascar. Viral metagenomic analysis of captive ruffed lemur oral swabs revealed the first complete genomes of papillomaviruses in lemurs representing three novel PV types, a putative new genus in Papillomaviridae, and a rare case of interspecies papillomavirus infection. Expanding across biogeographical sites and species, we characterized DNA viral communities – anelloviruses, cressdnaviruses, and bacteriophages – in oral, fecal, and blood samples of seven captive lemur species and passive drool samples of human caretakers. Turning to southeastern Madagascar, viral metagenomic analysis of lemur oral swabs revealed exceedingly low similarity of lemur adenovirus, papillomavirus, adeno-associated virus, and circovirus sequences with other primate viruses. Additionally, although positioned near primate-infecting lineages, lemur herpesvirus and polyomavirus sequences were highly divergent. Endemic and nonnative rodent viral sequences – adenovirus, herpesvirus, papillomavirus, parvovirus, polyomavirus, circovirus – were generally related to known rodent-infecting viral lineages with the exception of poxviruses in black rats. Lastly, focusing on a massive dataset of over 600 complete anellovirus genomes, we demonstrate the diversity of lemur and rodent anelloviruses and the impacts of demographic factors on anellovirus richness and community composition in black rats. Overall, the distinct evolutionary history of mammals on Madagascar has led to incredibly diverse DNA viruses as reflected in the viral communities of captive lemurs and natural lemur and rodent populations described in this dissertation.