Changes associated with Ebola virus adaptation to novel species

Abstract

Motivation: Ebola viruses are not pathogenic but can be adapted to replicate and cause disease in rodents. Here, we used a structural bioinformatics approach to analyze the mutations associated with Ebola virus adaptation to rodents to elucidate the determinants of host-specific Ebola virus pathogenicity. Results: We identified 33 different mutations associated with Ebola virus adaptation to rodents in the proteins GP, NP, L, VP24, and VP35. Only VP24, GP and NP were consistently found mutated in rodent-adapted Ebola virus strains. Fewer than five mutations in these genes seem to be required for the adaptation of Ebola viruses to a new species. The role of mutations in GP and NP is not clear. However, three VP24 mutations located in the protein interface with karyopherin a5 may enable VP24 to inhibit karyopherins and subsequently the host interferon response. Three further VP24 mutations change hydrogen bonding or cause conformational changes. Hence, there is evidence that few mutations including crucial mutations in VP24 enable Ebola virus adaptation to new hosts. Since Reston virus, the only non-human pathogenic Ebolavirus species circulates in pigs in Asia, this raises concerns that few mutations may result in novel human pathogenic Ebolaviruses.

Structural and Functional Aspects of Ebola Virus Proteins

“…Another study highlighted the significance of NP C-terminal domain (CTD) aa 641-739 (Figure 4) information of inclusion bodies and infectious virus-like particle (VLP) production [92]. Interestingly, laboratory data indicate that only point mutations in NP and L are required for virus adaptation to different species [93].…”

VP24 matrix proteins of eight filoviruses downregulate innate immune response by inhibiting the interferon-induced pathway

“…Filoviruses are zoonotic viruses, and spillover transmission to humans could lead to amino acid changes enabling these viruses to infect and spread in the human population. Evasion of immune responses is an important phenomenon during a virus life cycle, and especially VP24 protein seemed to accumulate amino acid changes during filoviral adaption to rodents [26]. The recent EBOV outbreaks and the newly discovered filoviruses emphasize the need for a better understanding of filovirus host cell interactions and the possible differences and similarities of the functions of viral proteins.…”

Structural risk analysis of a potential Ebola outbreak with respect to infrastructural aspects amid the current COVID-19 pandemic

“…In fact, recent data raise some concern with respect to the evolutionary changes in Ebola biology and the routes of transmission. Recent studies were able to demonstrate the pulmonary involvement of Ebola ( 18 ) and the ongoing adaptation of the virus to new species ( 19 ). Another new concerning development are reports of Ebola virus transmission by a selective group of individuals known as persistently infected survivors ( 20 ).…”