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Effects of Overexpression of the Egyptian Fruit Bat Innate Immune Genes on Filovirus Infections in the Host Cells.

ABSTRACT: Bats constitute a large and diverse group of mammals with unique characteristics. One of these is the ability of bats to maintain various pathogens, particularly viruses, without evidence of disease. The innate immune system has been implicated as one of the important components involved in this process. However, in contrast to the human innate immune system, little data is available for bats. In the present study we generated 23 fusion constructs of innate immune genes of Egyptian fruit bat (Rousettus aegyptiacus) with mCherry as a fluorescent reporter. We evaluated the effects of overexpressing these genes on the replication of Marburg and Ebola viruses in the Egyptian fruit bat cell line R06EJ. Both viruses were substantially inhibited by overexpression of type I, II and III interferons, as well as by DDX58 (RIG-I), IFIH1, and IRF1. Our observations suggest that the broad antiviral activity of these genes reported previously in human cells is conserved in Egyptian fruit bats and these possess anti-filovirus activities that may contribute to the efficient virus clearance.

SUBMITTER: Kuzmin IV

PROVIDER: S-EPMC9555311 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Effects of Overexpression of the Egyptian Fruit Bat Innate Immune Genes on Filovirus Infections in the Host Cells.

Kuzmin Ivan V IV Ramanathan Palaniappan P Basler Christopher F CF Bukreyev Alexander A

Frontiers in virology (Lausanne, Switzerland) 20211012

Bats constitute a large and diverse group of mammals with unique characteristics. One of these is the ability of bats to maintain various pathogens, particularly viruses, without evidence of disease. The innate immune system has been implicated as one of the important components involved in this process. However, in contrast to the human innate immune system, little data is available for bats. In the present study we generated 23 fusion constructs of innate immune genes of Egyptian fruit bat (<i ...[more]

PMID: 36237518

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Project description:In the family of fruit bats, Pteropodidae Gray, 1821, as in the third most diverse group of bats (Chiroptera), the bacterium of the genus Bartonella was detected in several species as well as in a few species of their insect ectoparasites in some tropical and sub-tropical regions of the Old World. The Egyptian fruit bat, Rousettus aegyptiacus (Geoffroy, 1810), is one of the most widespread fruit bats, occurring between South Africa, Senegal, and Pakistan. In this bat species, Candidatus Bartonella rousetti has been detected in three African populations in Nigeria, Kenya, and Zambia. This fruit bat, however, also occurs in the Palaearctic, an area isolating the species geographically and phylogenetically from the Afrotropical part of its distribution range. We screened the blood-sucking bat flies (family Nycteribiidae) from R. aegyptiacus for the presence of the Bartonella bacteria. A rich material of bat fly Eucampsipoda aegyptia (Macquart, 1850), a monoxenous ectoparasite of the Egyptian fruit bats, was collected at 26 localities in seven countries (Egypt, Iran, Jordan, Lebanon, Oman, United Arab Emirates, and Yemen) of the Middle East in 2007-2013. The DNA isolates from the bat flies were subjected to a three-marker (gltA, ssrA, and intergenic spacer region, ITS) multilocus sequence analysis. Based on the amplification of the fragment of ssrA gene by a real-time PCR, 65 E. aegyptia samples from 19 localities in all seven countries were positive for the bacteria. One to five Bartonella-positive individuals of E. aegyptia were collected per one individual of R. aegyptiacus. An analysis of the ITS and gltA genes indicated the presence of an uncultured Bartonella sp., belonging to the Cand. B. rousetti genogroup, identified from populations of the Egyptian fruit bat in Africa. These results support the hypothesis that Bartonella's diversity corresponds to its host's diversity (and phylogenetic structure). Specific lineages of pathogens are present in specific phylogenetic groups of bats.

Project description:BackgroundLittle is known of the biological significance and evolutionary maintenance of integrated non-retroviral RNA virus genes in eukaryotic host genomes. Here, we isolated novel filovirus-like genes from bat genomes and tested for evolutionary maintenance. We also estimated the age of filovirus VP35-like gene integrations and tested the phylogenetic hypotheses that there is a eutherian mammal clade and a marsupial/ebolavirus/Marburgvirus dichotomy for filoviruses.ResultsWe detected homologous copies of VP35-like and NP-like gene integrations in both Old World and New World species of Myotis (bats). We also detected previously unknown VP35-like genes in rodents that are positionally homologous. Comprehensive phylogenetic estimates for filovirus NP-like and VP35-like loci support two main clades with a marsupial and a rodent grouping within the ebolavirus/Lloviu virus/Marburgvirus clade. The concordance of VP35-like, NP-like and mitochondrial gene trees with the expected species tree supports the notion that the copies we examined are orthologs that predate the global spread and radiation of the genus Myotis. Parametric simulations were consistent with selective maintenance for the open reading frame (ORF) of VP35-like genes in Myotis. The ORF of the filovirus-like VP35 gene has been maintained in bat genomes for an estimated 13. 4 MY. ORFs were disrupted for the NP-like genes in Myotis. Likelihood ratio tests revealed that a model that accommodates positive selection is a significantly better fit to the data than a model that does not allow for positive selection for VP35-like sequences. Moreover, site-by-site analysis of selection using two methods indicated at least 25 sites in the VP35-like alignment are under positive selection in Myotis.ConclusionsOur results indicate that filovirus-like elements have significance beyond genomic imprints of prior infection. That is, there appears to be, or have been, functionally maintained copies of such genes in mammals. "Living fossils" of filoviruses appear to be selectively maintained in a diverse mammalian genus (Myotis).

Dataset Information

Effects of Overexpression of the Egyptian Fruit Bat Innate Immune Genes on Filovirus Infections in the Host Cells.

Publications

Effects of Overexpression of the Egyptian Fruit Bat Innate Immune Genes on Filovirus Infections in the Host Cells.

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