Elucidating mechanisms of viral hosting in bat reservoirs for emerging zoonotic disease

Abstract

Bats are the acknowledged reservoir hosts for several of the world’s most virulent

emerging zoonotic diseases, including Hendra and Nipah henipaviruses, SARS and

MERS coronaviruses, and Ebola and Marburg filoviruses. Bats appear to host these

viruses—which are highly pathogenic in other mammals—while experiencing little to no

ostensible morbidity or mortality, a phenomenon that has led researchers to question,

increasingly, are bats somehow ‘special’ in their capacity as pathogen hosts? Reviews of

the literature indicate that bats, which comprise the second-most speciose mammalian

order (Chiroptera) and make up ~20% of all mammalian diversity, host a

disproportionate number of zoonotic viruses (those viruses which transmit from wildlife

to human hosts) as compared with all other mammals.

This thesis explores the mechanisms by which bats host virulent infections, at

both within-host and cross-population levels. In Chapter One, I delve deeply into the

molecular biological underpinnings of bat metabolism, as relates to the evolution of

flight, the one characteristic, which—above all—distinguishes Chiropterans from other

mammals; I offer insights as to how such evolution might have shaped bat tolerance for,

specifically, intracellular (often viral) infections. In Chapter Two, I explore the

population-level dynamics of transmission for an intracellular bacterial infection in a

community of sympatric Madagascar fruit bats, highlighting the critical reliance of these

pathogens on species-specific host-parasite-vector relationships. In Chapter Three, I

model the age-structured dynamics of transmission of henipaviruses and filoviruses

infecting these same Madagascar fruit bats; I uncover a signature of elevated mortality

in seropositive bats, a noteworthy indication of “disease” in these seemingly “special”

viral hosts. In Chapter Four, I return once more to the molecular scale to model the

dynamics of within-host viral transmission, using data describing the spread of viral

infection across monolayers of bat cells. I highlight the critical reliance of bat cells on

perpetually primed innate immune responses—a unique feature in mammalian

immunity—to contain and control viral pathogenesis.

Bats are indeed special, it seems, in their capacity as viral hosts.