Non-structural genes of novel lemur adenoviruses reveal codivergence of virus and host.

Adenoviruses (AdVs) are important human and animal pathogens and are frequently used as vectors for gene therapy and vaccine delivery. Surprisingly, there are only scant data regarding primate AdV origin and evolution, especially in the most basal primate hosts. We detect and sequence AdVs from faeces of two Madagascan lemur species. Complete genome sequence analyses define a new AdV species with a particularly large gene encoding a protein of unknown function in the early gene region 3. Unexpectedly, the new AdV species is not most similar to human or other simian AdVs but to bat adenovirus C. Genome characterisation shows signals of virus-host codivergence in non-structural genes, which show lower diversity than structural genes. Outside a lemur species mixing zone, recombination less frequently separates structural genes, as in human adenovirus C. The evolutionary history of lemur AdVs likely involves both a host switch and codivergence with the lemur hosts.

A framework for testing the impact of co-infections on host gut microbiomes.

Parasitic infections disturb gut microbial communities beyond their natural range of variation, possibly leading to dysbiosis. Yet it remains underappreciated that most infections are accompanied by one or more co-infections and their collective impact is largely unexplored. Here we developed a framework illustrating changes to the host gut microbiome following single infections, and build on it by describing the neutral, synergistic or antagonistic impacts on microbial α- and ß-diversity expected from co-infections. We tested the framework on microbiome data from a non-human primate population co-infected with helminths and Adenovirus, and matched patterns reported in published studies to the introduced framework. In this case study, α-diversity of co-infected Malagasy mouse lemurs (Microcebus griseorufus) did not differ in comparison with that of singly infected or uninfected individuals, even though community composition captured with ß-diversity metrices changed significantly. Explicitly, we record stochastic changes in dispersion, a sign of dysbiosis, following the Anna-Karenina principle rather than deterministic shifts in the microbial gut community. From the literature review and our case study, neutral and synergistic impacts emerged as common outcomes from co-infections, wherein both shifts and dispersion of microbial communities following co-infections were often more severe than after a single infection alone, but microbial α-diversity was not universally altered. Important functions of the microbiome may also suffer from such heavily altered, though no less species-rich microbial community. Lastly, we pose the hypothesis that the reshuffling of host-associated microbial communities due to the impact of various, often coinciding parasitic infections may become a source of novel or zoonotic diseases.

Anthropogenic Disturbance Impacts Gut Microbiome Homeostasis in a Malagasy Primate.

Increasing anthropogenic disturbances in Madagascar are exerting constrains on endemic Malagasy lemurs and their habitats, with possible effects on their health and survival. An important component of health is the gut microbiome, which might be disrupted by various stressors associated with environmental change. We have studied the gut microbiome of gray-brown mouse lemurs (Microcebus griseorufus), one of the smallest Malagasy primates and an important model of the convergent evolution of diseases. We sampled two sites: one situated in a national park and the other consisting of a more disturbed site around human settlement. We found that more intense anthropogenic disturbances indeed disrupted the gut microbiome of this lemur species marked by a reduction in bacterial diversity and a shift in microbial community composition. Interestingly, we noted a decrease in beneficial bacteria (i.e., members of the Bacteroidaceae family) together with a slight increase in disease-associated bacteria (i.e., members of the Veillonellaceae family), and alterations in microbial metabolic functions. Because of the crucial services provided by the microbiome to pathogen resistance and host health, such negative alterations in the gut microbiome of mouse lemurs inhabiting anthropogenically disturbed habitats might render them susceptible to diseases and ultimately affecting their survival in the shrinking biodiversity seen in Madagascar. Gut microbiome analyses might thus serve as an early warning signal for pending threats to lemur populations.

Evidence of MHC class I and II influencing viral and helminth infection via the microbiome in a non-human primate.

Until recently, the study of major histocompability complex (MHC) mediated immunity has focused on the direct link between MHC diversity and susceptibility to parasite infection. However, MHC genes can also influence host health indirectly through the sculpting of the bacterial community that in turn shape immune responses. We investigated the links between MHC class I and II gene diversity gut microbiome diversity and micro- (adenovirus, AdV) and macro- (helminth) parasite infection probabilities in a wild population of non-human primates, mouse lemurs of Madagascar. This setup encompasses a plethora of underlying interactions between parasites, microbes and adaptive immunity in natural populations. Both MHC classes explained shifts in microbiome composition and the effect was driven by a few select microbial taxa. Among them were three taxa (Odoribacter, Campylobacter and Prevotellaceae-UCG-001) which were in turn linked to AdV and helminth infection status, correlative evidence of the indirect effect of the MHC via the microbiome. Our study provides support for the coupled role of MHC diversity and microbial flora as contributing factors of parasite infection.

Adenovirus infection is associated with altered gut microbial communities in a non-human primate.

Adenovirus (AdV) infections are one of the main causes of diarrhea in young children. Enteric AdVs probably disrupt gut microbial defences, which can result in diarrhea. To understand the role of the gut microbiome in AdV-induced pathologies, we investigated the gut microbiome of a naturally AdV-infected non-human primate species, the Malagasy mouse lemur (Microcebus griseorufus), which represents an important model in understanding the evolution of diseases. We observed that AdV infection is associated with disruption of the gut microbial community composition. In AdV+ lemurs, several commensal taxa essential for a healthy gut microbiome decreased, whereas genera containing potential pathogens, such as Neisseria, increased in abundance. Microbial co-occurrence networks revealed a loss of important microbial community interactions in AdV+ lemurs and an overrepresentation of Prevotellaceae. The observation of enteric virus-associated loss of commensal bacteria and associated shifts towards pathobionts may represent the missing link for a better understanding of AdV-induced effects in humans, and also for their potential as drivers of co-infections, an area of research that has been largely neglected so far.