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Assays for the Specific Growth Rate and Cell-binding Ability of Rotavirus
Published on: January 28, 2019
Full genome based sequence and structural characterization of an unusual group A rotavirus G12P[11] isolated from
Sujata S Ranshing1, Sarah S Cherian2, Megha S Agarwal2
1Enteric Viruses Group, ICMR-National Institute of Virology, Pune, India.
Insights
Neonatal rotavirus strains in India exhibit genetic reassortment, with unusual G12P[11] types. Structural analysis reveals variations impacting viral tropism in newborns.
Area of Science:
- Virology
- Genomics
- Structural Biology
Background:
- Rotavirus infections are a leading cause of severe diarrhea in infants globally.
- Neonatal intensive care units (NICUs) in Pune, India, have observed early rotavirus exposure and a prevalence of uncommon G12P[11] strains.
- Understanding the genetic makeup and structural properties of these neonatal strains is crucial for vaccine development and disease control.
Purpose of the Study:
- To perform whole genome sequencing and phylogenetic analysis of a naturally attenuated neonatal rotavirus strain (NIV-1740121).
- To investigate the genetic reassortment events within the strain.
- To analyze the structural variations in key viral proteins (VP7 and VP4) and their potential impact on receptor binding and tropism.
Main Methods:
- Whole genome sequencing of the neonatal rotavirus strain NIV-1740121.
- Phylogenetic analysis to determine the origin of individual genes.
- 3D structure modeling of VP7 and VP4 proteins.
- Visualization of receptor-glycan interactions for VP8* proteins.
Main Results:
- The NIV-1740121 strain resulted from multiple gene reassortment events.
- It contains genes from the ROTAVAC® vaccine strain, porcine rotavirus, and a G12 origin, within a human Wa-like backbone.
- Structural analysis indicated amino acid variations in VP7 neutralizing epitopes and similar glycan binding conformations in VP8* compared to other strains.
- The P[11] strains demonstrate age-restricted tropism in neonates.
Conclusions:
- The study elucidates the complex genetic mosaic of a neonatal rotavirus strain from India.
- Structural insights suggest mechanisms for altered protein interactions and host tropism.
- Findings contribute to understanding the epidemiology and evolution of rotaviruses in neonates, informing public health strategies.
Abstract:
Studies conducted at neonatal intensive care units in Pune, western India, suggested early exposure to rotaviruses and predominance of unusual human-bovine-like G12P[11] strains. The whole genome sequencing and phylogenetic analyses of a naturally attenuated, culture adapted neonatal strain, (NIV-1740121) revealed multiple-gene reassortment events, containing ROTAVAC® vaccine strain, 116E-like VP4, VP6, NSP3, NSP5 genes, VP7 gene of G12 origin and VP3 gene of porcine ancestry in a human Wa-like backbone. Analysis of 3D structure modeling of the VP7 and VP4 proteins with respect to 116E suggested amino acid variations in the major neutralizing epitopes of VP7, contributed to a modified charge density. Visualization of receptor-glycan interaction structures of NIV-1740121 and 116E VP8* showed type I glycan binds with a similar conformation at the same active site as represented in the available crystal structure of G10P[11] VP8*. The study adds to the knowledge of age restricted tropism of P[11] strains in neonates.

