North American bats and their viruses: The effect of stressors on persistent infections and viral shedding
Subudhi, Sonu 1989-
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There is direct or circumstantial evidence that several viruses that cause no obvious disease in bats have spilled over into humans and other species causing serious and often fatal disease. The reasons for the lack of disease in bats or for the spillover of these viruses from bats are poorly understood. While there is considerable literature on the interactions of these viruses with their secondary hosts or their surrogates, little is known about the interactions of bat viruses in their natural hosts. We used a coronavirus detected in little brown bat (Myotis lucifugus) and a herpesvirus, detected in the big brown bat (Eptesicus fuscus), as models to understand the factors that might alter bat-virus relationships. We demonstrated that a coronavirus (Myotis lucifugus coronavirus – Myl-CoV) detected in the intestines of little brown bats, could persist in them during the 4 months of hibernation. Using this coronavirus-bat model, we showed that the stress of fungal infection by Pseudogymnoascus destructans (Pd), which causes bat white-nose syndrome (WNS), led to a 60-fold increase in viral replication in intestines than bats with virus alone. Increased viral replication correlated with the severity of Pd-related pathology and the intestine of fungus-infected bats showed changes in gene expression suggesting suppressed innate antiviral response and increased apoptotic responses. Our results suggest that the systemic effects of WNS leads to a resurgence of virus replication and increases the potential of virus shedding. Using a bat cell culture model, we showed that viral persistence could be disrupted by artificially suppressing the host cell’s antiviral response and was mediated through similar pathways that were observed during in-vivo experiments. To ascertain whether the effect of stressor could disrupt viral persistence in other bat-virus relationships, I studied the big brown bat herpesvirus. As herpesviruses inherently establish life-long latent infections in their hosts and reactivate periodically in response to stress, we used this model to study the effects of natural stressors on the bat-virus relationship. We characterized the herpesvirus and developed techniques for detecting the virus as well as for monitoring the adaptive antibody response against the virus. We showed that the bat gammaherpesvirus reactivates at the end of hibernation and was accompanied by a lower antibody level, which subsequently increased upon arousal. Our studies on coronavirus and herpesvirus show that bats have a long-term balanced and benign relationships with viruses and a variety of stressors could disrupt this balance allowing an increase in viral replication.
DegreeDoctor of Philosophy (Ph.D.)
CommitteeZhou, Yan; Falzarano, Darryl; Bollinger, Trent K; Rubin, Joseph
Copyright DateMay 2019