Analysis of coevolution in nonstructural proteins of chikungunya virus
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RESEARCH
Open Access
Analysis of coevolution in nonstructural proteins of chikungunya virus Jaspreet Jain, Kalika Mathur, Jatin Shrinet, Raj K. Bhatnagar and Sujatha Sunil*
Abstract Background: RNA viruses are characterized by high rate of mutations mainly due to the lack of proofreading repair activities associated with its RNA-dependent RNA-polymerase (RdRp). In case of arboviruses, this phenomenon has lead to the existence of mixed population of genomic variants within the host called quasi-species. The stability of strains within the quasi-species lies on mutations that are positively selected which in turn depend on whether these mutations are beneficial in either or both hosts. Coevolution of amino acids (aa) is one phenomenon that leads to establishment of favorable traits in viruses and leading to their fitness. Results: Fourteen CHIKV clinical samples collected over three years were subjected to RT-PCR, the four non-structural genes amplified and subjected to various genetic analyses. Coevolution analysis showed 30 aa pairs coevolving in nsP1, 23 aa pairs coevolving in nsP2, 239 in nsP3 and 46 aa coevolving pairs in nsP4 when each non-structural protein was considered independently. Further analysis showed that 705 amino acids pairs of the non-structural polyproteins coevolved together with a correlation coefficient of ≥0.5. Functional relevance of these coevolving amino acids in all the nonstructural proteins of CHIKV were predicted using Eukaryotic Linear Motifs (ELMs) of human. Conclusions: The present study was undertaken to study co-evolving amino acids in the non-structural proteins of chikungunya virus (CHIKV), an important arbovirus. It was observed that several amino acids residues were coevolving and shared common functions. Keywords: Chikungunya virus, Coevolution, Nonstructural proteins, Eukaryotic linear motifs
Background Coevolution at the molecular level is an established phenomenon exhibited by organisms in order to optimize their physiological performance and serve as an effective determinant of fitness [1, 2]. Coevolution refers to synchronized changes that organisms or proteins undergo and can occur with respect to pathogen-host [3], as well as within the organism [4, 5], often revealing functional coordination regarding the interacting pairs. One of the most compelling examples of coevolution of host and pathogen can be witnessed in the retrovirus, mainly because of their tolerance to mutagenesis [6]. Studies in HIV have shown that drug resistance is manifested by coevolution of proteins in the virus under drug selective pressure [7, 8]. Selection advantage of coevolution may ultimately result in recombination events [9]. * Correspondence: [email protected] Insect Resistance Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India
Chikungunya virus (CHIKV) is a re-emerging arbovirus belonging to family Togaviridae. Known to exist as mixed populations of genomic variants, known as quasispecies, these variants confer phenotypic plasticity and
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