Crossing scales to predict and prevent bat virus zoonoses in a Madagascar ecosystem

The wide-reaching impacts of the COVID-19 pandemic highlight the extreme threat posed by the cross-species
emergence of zoonotic pathogens. Bats (order: Chiroptera) are the natural reservoir hosts for the majority of
the world’s most virulent zoonotic viruses, including Hendra and Nipah henipaviruses, Ebola and Marburg
filoviruses, and SARS, MERS, and now SARS-CoV-2 coronaviruses. Remarkably, bats exhibit little
demonstrable disease upon infection with viruses that cause extreme pathology in other mammals, likely in
part due to their unique anti-inflammatory molecular adaptations, which are thought to have evolved to mitigate
the accumulation of physiological damage accrued during flight. Surprisingly, isolated island bat communities
around the world support the endemic circulation of numerous viruses in populations below the critical
community size required for persistence of related pathogens in other hosts. Since cross-species spillover of
several bat-borne viruses bears a distinctive seasonal signature, coincident with the timing of reproductive and
nutritional stress for the bat hosts in question, disentangling the mechanisms governing the transmission,
circulation, and persistence of these viruses in wild bat populations is of critical public health interest. In part
with the research initiatives proposed here, we will use molecular and serological tools to develop a
longitudinal time series of immunological and infection data for henipaviruses and coronaviruses circulating in
wild fruit bats in Madagascar, leveraging samples collected in our longterm wildlife surveillance effort. Bats are
widely consumed as a source of human food in Madagascar, and preliminary data from our research group
demonstrates serological signatures of prior human exposure to these zoonotic viruses across the island. We
propose to fit disparate dynamical models to the resulting population-level data in order to distinguish
mechanisms underpinning seasonal viral shedding pulses and concomitant transmission in these bat hosts. In
addition to population-level studies, we will also construct within-host models of viral control in a single bat
immune system, which we will fit to experimental infection data from Betacoronavirus-challenged bats in the
laboratory, with the aim of deciphering the mechanisms which motivate viral shedding. Our project aims to
simultaneously develop molecular tools of bat cell lines and viruses with which to support within-host studies in
our own Madagascar system. Finally, we will build on population-level and within-host studies to model and
implement a vaccine intervention designed to eradicate circulating henipavirus from a test-population of
Madagascar fruit bats. Broadly, our project aims to use a uniquely integrative combination of field, molecular,
and modeling tools to enable the prediction and prevention of bat virus spillover events before they occur.

Grant Number: 7DP2AI171120-04
NIH Institute/Center: NIH
Principal Investigator: Cara Brook