Amy T. Gilbert

New World Bats Harbor Diverse Influenza A Viruses

Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.

A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special?

Bats are the natural reservoirs of a number of high-impact viral zoonoses. We present a quantitative analysis to address the hypothesis that bats are unique in their propensity to host zoonotic viruses based on a comparison with rodents, another important host order. We found that bats indeed host more zoonotic viruses per species than rodents, and we identified life-history and ecological factors that promote zoonotic viral richness. More zoonotic viruses are hosted by species whose distributions overlap with a greater number of other species in the same taxonomic order (sympatry). Specifically in bats, there was evidence for increased zoonotic viral richness in species with smaller litters (one young), greater longevity and more litters per year. Furthermore, our results point to a new hypothesis to explain in part why bats host more zoonotic viruses per species: the stronger effect of sympatry in bats and more viruses shared between bat species suggests that interspecific transmission is more prevalent among bats than among rodents. Although bats host more zoonotic viruses per species, the total number of zoonotic viruses identified in bats (61) was lower than in rodents (68), a result of there being approximately twice the number of rodent species as bat species. Therefore, rodents should still be a serious concern as reservoirs of emerging viruses. These findings shed light on disease emergence and perpetuation mechanisms and may help lead to a predictive framework for identifying future emerging infectious virus reservoirs.

Bats are a major natural reservoir for hepaciviruses and pegiviruses

Although there are over 1,150 bat species worldwide, the diversity of viruses harbored by bats has only recently come into focus as a result of expanded wildlife surveillance. Such surveys are of importance in determining the potential for novel viruses to emerge in humans, and for optimal management of bats and their habitats. To enhance our knowledge of the viral diversity present in bats, we initially surveyed 415 sera from African and Central American bats. Unbiased high-throughput sequencing revealed the presence of a highly diverse group of bat-derived viruses related to hepaciviruses and pegiviruses within the family Flaviridae. Subsequent PCR screening of 1,258 bat specimens collected worldwide indicated the presence of these viruses also in North America and Asia. A total of 83 bat-derived viruses were identified, representing an infection rate of nearly 5%. Evolutionary analyses revealed that all known hepaciviruses and pegiviruses, including those previously documented in humans and other primates, fall within the phylogenetic diversity of the bat-derived viruses described here. The prevalence, unprecedented viral biodiversity, phylogenetic divergence, and worldwide distribution of the bat-derived viruses suggest that bats are a major and ancient natural reservoir for both hepaciviruses and pegiviruses and provide insights into the evolutionary history of hepatitis C virus and the human GB viruses.

Ecology of Zoonotic Infectious Diseases in Bats: Current Knowledge and Future Directions

Bats are hosts to a range of zoonotic and potentially zoonotic pathogens. Human activities that increase exposure to bats will likely increase the opportunity for infections to spill over in the future. Ecological drivers of pathogen spillover and emergence in novel hosts, including humans, involve a complex mixture of processes, and understanding these complexities may aid in predicting spillover. In particular, only once the pathogen and host ecologies are known can the impacts of anthropogenic changes be fully appreciated. Cross‐disciplinary approaches are required to understand how host and pathogen ecology interact. Bats differ from other sylvatic disease reservoirs because of their unique and diverse lifestyles, including their ability to fly, often highly gregarious social structures, long lifespans and low fecundity rates. We highlight how these traits may affect infection dynamics and how both host and pathogen traits may interact to affect infection dynamics. We identify key questions relating to the ecology of infectious diseases in bats and propose that a combination of field and laboratory studies are needed to create data‐driven mechanistic models to elucidate those aspects of bat ecology that are most critical to the dynamics of emerging bat viruses. If commonalities can be found, then predicting the dynamics of newly emerging diseases may be possible. This modelling approach will be particularly important in scenarios when population surveillance data are unavailable and when it is unclear which aspects of host ecology are driving infection dynamics.

Deciphering Serology to Understand the Ecology of Infectious Diseases in Wildlife

The ecology of infectious disease in wildlife has become a pivotal theme in animal and public health. Studies of infectious disease ecology rely on robust surveillance of pathogens in reservoir hosts, often based on serology, which is the detection of specific antibodies in the blood and is used to infer infection history. However, serological data can be inaccurate for inference to infection history for a variety of reasons. Two major aspects in any serological test can substantially impact results and interpretation of antibody prevalence data: cross-reactivity and cut-off thresholds used to discriminate positive and negative reactions. Given the ubiquitous use of serology as a tool for surveillance and epidemiological modeling of wildlife diseases, it is imperative to consider the strengths and limitations of serological test methodologies and interpretation of results, particularly when using data that may affect management and policy for the prevention and control of infectious diseases in wildlife. Greater consideration of population age structure and cohort representation, serological test suitability and standardized sample collection protocols can ensure that reliable data are obtained for downstream modeling applications to characterize, and evaluate interventions for, wildlife disease systems.

Evidence of rabies virus exposure among humans in the Peruvian Amazon.

In May of 2010, two communities (Truenococha and Santa Marta) reported to be at risk of vampire bat depredation were surveyed in the Province Datem del Marañón in the Loreto Department of Perú. Risk factors for bat exposure included age less than or equal to 25 years and owning animals that had been bitten by bats. Rabies virus neutralizing antibodies (rVNAs) were detected in 11% (7 of 63) of human sera tested. Rabies virus ribonucleoprotein (RNP) immunoglobulin G (IgG) antibodies were detected in the sera of three individuals, two of whom were also seropositive for rVNA. Rabies virus RNP IgM antibodies were detected in one respondent with no evidence of rVNA or RNP IgG antibodies. Because one respondent with positive rVNA results reported prior vaccination and 86% (six of seven) of rVNA-positive respondents reported being bitten by bats, these data suggest nonfatal exposure of persons to rabies virus, which is likely associated with vampire bat depredation.

Discovery of diverse polyomaviruses in bats and the evolutionary history of the Polyomaviridae

Polyomaviruses (PyVs) have been identified in a wide range of avian and mammalian species. However, little is known about their occurrence, genetic diversity and evolutionary history in bats, even though bats are important reservoirs for many emerging viral pathogens. This study screened 380 specimens from 35 bat species from Kenya and Guatemala for the presence of PyVs by semi-nested pan-PyV PCR assays. PyV DNA was detected in 24 of the 380 bat specimens. Phylogenetic analysis revealed that the bat PyV sequences formed 12 distinct lineages. Full-genome sequences were obtained for seven representative lineages and possessed similar genomic features to known PyVs. Strikingly, this evolutionary analysis revealed that the bat PyVs were paraphyletic, suggestive of multiple species jumps between bats and other mammalian species, such that the theory of virus-host co-divergence for mammalian PyVs as a whole could be rejected. In addition, evidence was found for strong heterogeneity in evolutionary rate and potential recombination in a number of PyV complete genomes, which complicates both phylogenetic analysis and virus classification. In summary, this study revealed that bats are important reservoirs of PyVs and that these viruses have a complex evolutionary history.

Prevalence and Diversity of Bartonella spp. in Bats in Peru

Bartonella infections were investigated in bats in the Amazon part of Peru. A total of 112 bats belonging to 19 species were surveyed. Bartonella bacteria were cultured from 24.1% of the bats (27/112). Infection rates ranged from 0% to 100% per bat species. Phylogenetic analyses of gltA of the Bartonella isolates revealed 21 genetic variants clustering into 13 divergent phylogroups. Some Bartonella strains were shared by bats of multiple species, and bats of some species were infected with multiple Bartonella strains, showing no evident specific Bartonella sp.-bat relationships. Rarely found in other bat species, the Bartonella strains of phylogroups I and III discovered from the common vampire bats (Desmodus rotundus) were more specific to the host bat species, suggesting some level of host specificity.

Transmission or within-host dynamics driving pulses of zoonotic viruses in reservoir-host populations

Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host–pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife.

Network analysis of host–virus communities in bats and rodents reveals determinants of cross‐species transmission

Abstract Bats are natural reservoirs of several important emerging viruses. Cross‐species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross‐species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence.