Analysis of coevolution in nonstructural proteins of chikungunya virus

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.

Optimization of commercially available Zika virus antibodies for use in a laboratory‐developed immunohistochemical assay

“…To determine the cross‐reactivity profile of the antibodies, each commercially available ZIKV antibody was tested against dengue virus (serogroups 1–4), West Nile virus, Japanese encephalitis virus, yellow fever virus, and chikungunya virus using the established optimal conditions (Table ). Chikungunya virus belongs to the family Togaviridae but shares a similar geographic distribution and clinical presentation to dengue and ZIKV , and therefore was included in the cross‐reactivity analysis.…”

The Putative Roles and Functions of Indel, Repetition and Duplication Events in Alphavirus Non-Structural Protein 3 Hypervariable Domain (nsP3 HVD) in Evolution, Viability and Re-Emergence

“…The deletions arose as the result of CHIKV (Asian) evolutionary adaptation to the specific local setting; for example, the CHIKV (Asian) MY/06/37348 and MY/06/37350 were isolated during a local CHIKV outbreak in Bagan Panchor Perak, Malaysia, in 2006 [225,237,250]. In addition, based on the human eukaryotic linear motif (ELM) predictions, it has been suggested that the deletion motifs might play a role in phosphorylation and virus stability [242]. However, the biological consequence(s) of the nsP3 HVD deletion event still need to be identified [237], and wet lab experiments are needed to deepen our understanding of the role of these deletion motifs in both alphaviruses and their hosts [242].…”

“…In addition, based on the human eukaryotic linear motif (ELM) predictions, it has been suggested that the deletion motifs might play a role in phosphorylation and virus stability [242]. However, the biological consequence(s) of the nsP3 HVD deletion event still need to be identified [237], and wet lab experiments are needed to deepen our understanding of the role of these deletion motifs in both alphaviruses and their hosts [242].…”

The medicinal chemistry of Chikungunya virus

“…11,[32][33][34] Basically, CHIKV illness severe joint pain in the ankles, fingers, toes, elbow, knees, and wrists. 38,39 In general, CHIKV attacks fibroblasts, suggesting its involvement with muscles, joints, and skin connective tissues. [35][36][37] In 40% of patients were found to still have anti-CHIKV immunoglobulin M (IgM), eighteen months after disease onset.…”