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Bats are “blind” to the deadly effects of viruses

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Science Immunology  01 Jun 2018:
Vol. 3, Issue 24, eaau2559
DOI: 10.1126/sciimmunol.aau2259

Abstract

Bats that harbor lethal viruses avoid disease through an evolved antiviral defense strategy that leverages tolerance for infections.

Department of Neurology, Human and Translational Immunology Program, Yale School of Medicine, New Haven, CT 06520, USA. Email: kevin.oconnor@yale.edu

Humans infected with a filovirus, such as the Marburg virus, face severe illness that can include uncontrollable bleeding (hemorrhage), high fever, multiple organ failure, and in many instances death. A natural reservoir for the Marburg virus is Rousettus aegyptiacus, the Egyptian fruit bat. An intriguing detail regarding bats infected with highly lethal viruses is that they are unique in their hosting duties: Infected bats don’t get sick.

It’s thought that differences in the immune system of bats, relative to other mammals, underpin their ability to control insidious intruders. Specific details, however, have been lacking. Pavlovich and co-authors used a hybrid short- and long-read sequencing strategy to generate a high-resolution draft genome of the Egyptian fruit bat; it is the most contiguous bat genome assembled to date. Their investigation gave considerable attention to the study of immune-related genes, given the unique response these bats have toward viral infection. The research team observed conspicuous evolutionary positive selection and large expansion of immune gene families, including major histocompatibility complex class I genes. Natural killer (NK) cell receptors were also expanded and remarkable in that many displayed both activating and inhibitory interaction motifs. Transcriptomics suggested that several NK receptors with inhibitory signaling characteristics were expressed at elevated levels. A number of type I interferon (IFN) genes were also expanded. Interestingly, twenty-two IFN-ω gene copies were found in the bats (humans have only one). In vitro experiments suggest that at least one selected member (IFN-ω4) has antiviral effects against infection. These collective results support the team’s hypothesis that bats tolerate viral infections by softening the proinflammatory responses that play key roles in the damage that occurs in other infected mammals.

Although these findings are seminal, there is much follow-up work to do. Numerous functional studies are required to evaluate whether the immune molecules identified in this study have an impact on the ability to host these viruses while escaping damaging inflammation and consequential injury.

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