Abstract
BackgroundRNA 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.ResultsFourteen 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.ConclusionsThe 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.
Highlights
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)
The results obtained in the present study revealed important intra-molecular coevolving aa residues of the replication complex of chikungunya virus (CHIKV)
Blood was drawn from these patients, sera separated and subjected to ELISA for testing the presence of chikungunya virus IgM antibodies using IgM capture ELISA kits supplied by National Institute of Virology (NIV), Pune
Summary
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). 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. 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]. Studies in HIV have shown that drug resistance is manifested by coevolution of proteins in the virus under drug selective pressure [7, 8]. Owing to its complicated life cycle that includes its survival in two disparate hosts, one invertebrate and the other vertebrate, several studies have be devoted to understand arbovirus fitness determinants [13,14,15] including host-specific fitness benefits [16, 17]
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