Going to Bat(s) for Studies of Disease Tolerance

Abstract

A majority of viruses that have caused recent epidemics with high lethality rates in people, are zoonoses originating from wildlife. Among them are filoviruses (e.g., Marburg, Ebola), coronaviruses (e.g., SARS, MERS), henipaviruses (e.g., Hendra, Nipah) which share the common features that they are all RNA viruses, and that a dysregulated immune response is an important contributor to the tissue damage and hence pathogenicity that results from infection in humans. Intriguingly, these viruses also all originate from bat reservoirs. Bats have been shown to have a greater mean viral richness than predicted by their phylogenetic distance from humans, their geographic range, or their presence in urban areas, suggesting other traits must explain why bats harbor a greater number of zoonotic viruses than other mammals. Bats are highly unusual among mammals in other ways as well. Not only are they the only mammals capable of powered flight, they have extraordinarily long life spans, with little detectable increases in mortality or senescence until high ages. Their physiology likely impacted their history of pathogen exposure and necessitated adaptations that may have also affected immune signaling pathways. Do our life history traits make us susceptible to generating damaging immune responses to RNA viruses or does the physiology of bats make them particularly tolerant or resistant? Understanding what immune mechanisms enable bats to coexist with RNA viruses may provide critical fundamental insights into how to achieve greater resilience in humans.

Coronaviruses and Immunosuppressed Patients: The Facts During the Third Epidemic

“…It has been postulated that the reason why bats are the natural, healthy reservoir of these viruses may reside in their immune tolerance. (5,6) These aspects may be relevant when it comes to infection of an immunocompromised host, potentially protected by a weaker immune response against the infection.…”

Calu-3 cells are largely resistant to entry driven by filovirus glycoproteins and the entry defect can be rescued by directed expression of DC-SIGN or cathepsin L

“…(Kuhn, 2017). There is compelling evidence that all members of the three genera circulate in bats, which are believed to serve as their natural reservoir, and that zoonotic transmissions of most of these viruses to humans can induce severe disease (Mandl et al, 2018;Olival and Hayman, 2014). Multiple filovirus outbreaks in Africa were recorded during the last 52 years and usually entailed less than 500 cases (Centers for Disease Control and Prevention, 2018).…”

Virus-Like Particles as an Instrument of Vaccine Production

“…The interest in recombinant vaccines is a consequence of the emergence of new infectious diseases, most often zoonotic ones. Among them are the outbreaks of human diseases caused by the Ebola virus, Zika virus, Marburg virus, the Middle East respiratory syndrome, and severe acute respiratory syndrome coronaviruses [3]. Oncology also places great hopes in recombinant vaccines, which may help to overcome immune tolerance in the case of cancer treatment [4].…”