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Asymptomatic Infection of Marburg Virus Reservoir Bats Is Explained by a Strategy of Immunoprotective Disease Tolerance
- Source :
- Current Biology. 31:257-270.e5
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Marburg virus (MARV) is among the most virulent pathogens of primates, including humans. Contributors to severe MARV disease include immune response suppression and inflammatory gene dysregulation (“cytokine storm”), leading to systemic damage and often death. Conversely, MARV causes little to no clinical disease in its reservoir host, the Egyptian rousette bat (ERB). Previous genomic and in vitro data suggest that a tolerant ERB immune response may underlie MARV avirulence, but no significant examination of this response in vivo yet exists. Here, using colony-bred ERBs inoculated with a bat isolate of MARV, we use species-specific antibodies and an immune gene probe array (NanoString) to temporally characterize the transcriptional host response at sites of MARV replication relevant to primate pathogenesis and immunity, including CD14+ monocytes/macrophages, critical immune response mediators, primary MARV targets, and skin at the inoculation site, where highest viral loads and initial engagement of antiviral defenses are expected. Our analysis shows that ERBs upregulate canonical antiviral genes typical of mammalian systems, such as ISG15, IFIT1, and OAS3, yet demonstrate a remarkable lack of significant induction of proinflammatory genes classically implicated in primate filoviral pathogenesis, including CCL8, FAS, and IL6. Together, these findings offer the first in vivo functional evidence for disease tolerance as an immunological mechanism by which the bat reservoir asymptomatically hosts MARV. More broadly, these data highlight factors determining disparate outcomes between reservoir and spillover hosts and defensive strategies likely utilized by bat hosts of other emerging pathogens, knowledge that may guide development of effective antiviral therapies.
- Subjects :
- filovirus
Male
0301 basic medicine
CD14
bat
Disease
immune response
Monocytes
General Biochemistry, Genetics and Molecular Biology
Proinflammatory cytokine
03 medical and health sciences
0302 clinical medicine
Immune system
Immunity
Chiroptera
Immune Tolerance
medicine
Animals
Humans
reservoir host
Marburg Virus Disease
ddc:610
emerging zoonotic pathogen
Asymptomatic Infections
disease tolerance
Marburg virus
Disease Reservoirs
virus-host interaction
biology
medicine.disease
ISG15
Virology
030104 developmental biology
Gene Expression Regulation
Marburgvirus
monocyte
Host-Pathogen Interactions
gene expression
biology.protein
Female
Antibody
610 Medizin und Gesundheit
General Agricultural and Biological Sciences
Cytokine storm
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 09609822
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Current Biology
- Accession number :
- edsair.doi.dedup.....d0beb3c0d1f4cb6b204c2c607772eb6b