Abstract
It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs) have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35) is found in the little brown bat (Myotis lucifugus) genome. Putative mlEFL35-derived protein (mlEFL35p) contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN) production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication. In this study, we transiently expressed mlEFL35p in human kidney cells and investigated its biological functions. We first found that mlEFL35p was coimmunoprecipitated with itself and ebolavirus VP35s but not with the viral nucleoprotein. Then the biological functions of mlEFL35p were analyzed by comparing it to ebolavirus VP35s. We found that the expression of mlEFL35p significantly inhibited human IFN-β promoter activity as well as VP35s. By contrast, expression of mlEFL35p did not support viral RNA transcription/replication and indeed slightly decrease the reporter gene expression in a minigenome assay. These results suggest that mlEFL35p potentially acts as an IFN antagonist but not a polymerase cofactor.
Highlights
Ebolaviruses are members of the family Filoviridae and cause severe hemorrhagic fever in humans and nonhuman primates
We first confirmed that mlEFL35p showed sequence similarities to ebolavirus VP35s with low expectation values with the highest score given by Reston virus (RESTV) VP35 (Table 1)
We compared amino acid residues involved in three subdomains mapped on the Ebola virus (EBOV) and RESTV VP35 sequences [31, 33,34,35,36]: the N-terminal domain containing the NP binding peptide (NPBP) at amino acid positions 20–48, the middle oligomerization domain at amino acid positions 82– 118 which is required for VP35 homo-oligomerization, and the C-terminal domain, which is called the IFN inhibitory domain (IID), at amino acid positions 220–340 (Fig 1)
Summary
Ebolaviruses are members of the family Filoviridae and cause severe hemorrhagic fever in humans and nonhuman primates. Five distinct species are known in the genus Ebolavirus: Zaire ebolavirus, Sudan ebolavirus, Taï Forest ebolavirus, Bundibugyo ebolavirus, and Reston. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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