Coding-Gene Coevolution Analysis of Rotavirus Proteins: A Bioinformatics and Statistical Approach

Abstract

Rotavirus remains a major cause of diarrhea in infants and young children worldwide. The permanent emergence of new genotypes puts the potential effectiveness of vaccines under serious question. The distribution of unusual genotypes subject to viral fitness is influenced by interactions among viral proteins. The present work aimed at analyzing the genetic constellation and the coevolution of rotavirus coding genes for the available rotavirus genotypes. Seventy-two full genome sequences of different genetic constellations were analyzed using a genetic algorithm. The results revealed an extensive genome-wide covariance network among the 12 viral proteins. Altogether, the emergence of new genotypes represents a challenge to the outcome and success of vaccination and the coevolutionary analysis of rotavirus proteins may boost efforts to better understand the interaction networks of proteins during viral replication/transcription.

New Insights into the Effect of Residue Mutations on the Rotavirus VP1 Function Using Molecular Dynamic Simulations

“…For RVA replication, VP1 is an RNA-directed RNA polymerase (RdRp) and can be considered the masterpiece for viral replication. We reported that most of the coevolving residues in VP1 are located in the RNA entry tunnel . Additional structural analysis of RVA proteins upon mutations may enhance our ability to better understand the role of residues in the entry tunnel of RVA VP1 in viral replication.…”

“…It is a significant cause of childhood gastroenteritis and accounts for ∼450,000 deaths annually, most occurring in developing countries . RVA also causes a great economic loss to the livestock industry worldwide, mostly in the developing countries. , In our previous work, we reported a complex network of coevolving residues for RVA genes of different genetic constellations using advanced genomic analysis . For RVA replication, VP1 is an RNA-directed RNA polymerase (RdRp) and can be considered the masterpiece for viral replication.…”

“…2,3 In our previous work, we reported a complex network of coevolving residues for RVA genes of different genetic constellations using advanced genomic analysis. 4 For RVA replication, VP1 is an RNA-directed RNA polymerase (RdRp) and can be considered the masterpiece for viral replication. We reported that most of the coevolving residues in VP1 are located in the RNA entry tunnel.…”

“…We reported that most of the coevolving residues in VP1 are located in the RNA entry tunnel. 4 Additional structural analysis of RVA proteins upon mutations may enhance our ability to better understand the role of residues in the entry tunnel of RVA VP1 in viral replication. In the presence of other proteins, such as VP2, VP1 is involved in both transcription and genome replication/ packaging.…”