title: Ebolavirus evolves in human to minimize the detection by immune cells by accumulating adaptive mutations.
abstract: The current outbreak of Zaire ebolavirus (EBOV) lasted longer than the previous outbreaks and there is as yet no proven treatment or vaccine available. Understanding host immune pressure and associated EBOV immune evasion that drive the evolution of EBOV is vital for diagnosis as well as designing a highly effective vaccine. The aim of this study was to deduce adaptive selection pressure acting on each amino acid sites of EBOV responsible for the recent 2014 outbreak. Multiple statistical methods employed in the study include SLAC, FEL, REL, IFEL, FUBAR and MEME. Results show that a total of 11 amino acid sites from sGP and ssGP, and 14 sites from NP, VP40, VP24 and L proteins were inferred as positively and negatively selected, respectively. Overall, the function of 11 out of 25 amino acid sites under selection pressure exactly found to be involved in T cell and B-cell epitopes. We identified that the EBOV had evolved through purifying selection pressure, which is a predictor that is known to aid the virus to adapt better to the human host and subsequently reduce the efficiency of existing immunity. Furthermore, computational RNA structure prediction showed that the three synonymous nucleotide mutations in NP gene altered the RNA secondary structure and optimal base-pairing energy, implicating a possible effect on genome replication. Here, we have provided evidence that the EBOV strains involved in the recent 2014 outbreak have evolved to minimize the detection by T and B cells by accumulating adaptive mutations to increase the survival fitness.
authors.affiliation: Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, 560 012 India.
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Ramaiah
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 USA ; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048 USA ; Department of Surgery, University of California at Los Angeles, Los Angeles, CA 90095 USA.
authors.forename: Vaithilingaraja
authors.initials: V
authors.lastname: Arumugaswami
keywords: Immune evasion; Natural selection; Vaccine; Zaire ebolavirus