TY - JOUR
T1 - Genomic Analysis of G2P[4] Group A Rotaviruses in Zambia Reveals Positive Selection in Amino Acid Site 7 of Viral Protein 3
AU - Mwangi, Peter N.
AU - Potgieter, Robyn Lee
AU - Simwaka, Julia
AU - Mpabalwani, Evans M.
AU - Mwenda, Jason M.
AU - Mogotsi, Milton T.
AU - Magagula, Nonkululeko
AU - Esona, Mathew D.
AU - Steele, A. Duncan
AU - Seheri, Mapaseka L.
AU - Nyaga, Martin M.
N1 - Funding Information:
This research was principally funded by a World Health Organization (WHO) grant awarded to M.M.N (Reference 2022/1252000-0). Additional grants from the Bill and Melinda Gates Foundation (BMGF-OPP1180423_2017), the South African Medical Research Foundation through the Self-Initiated Research grant, the National Research Foundation (NRF-120814), and the Poliomyelitis Research Foundation (PRF-19/16 awarded to M.M.N. and PRF 21/77 awarded to P.N.M.). The views and opinions expressed in this article are not necessarily those of the funding and affiliated institutions but solely of the authors of this publication.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/2
Y1 - 2023/2
N2 - The G2P[4] genotype is among the rotavirus strains that circulate commonly in humans. Several countries have reported its immediate upsurge after the introduction of rotavirus vaccination, raising concern about sub-optimal vaccine effectiveness against this genotype in the long term. This study aimed to gain insight into the evolution of post-vaccine Zambian G2P[4] group A rotavirus (RVA) strains and their overall genetic make-up by analysis of sequence alignments at the amino acid (AA) level. Twenty-nine Zambian G2P[4] rotavirus strains were subjected to whole-genome sequencing using the Illumina MiSeq® platform. All the strains exhibited the typical DS-1-like genotype constellation, and the nucleotide sequences of the 11 genome segments showed high nucleotide similarities (>97%). Phylogenetic analyses together with representative global G2P[4] RVA showed that Zambian strains clustered into human lineages IV (for VP2, VP4, VP7, NSP1, and NSP5), V (for VP1, VP3, VP6, NSP2, and NSP3), and XXIII (for NSP4). The AA differences between the lineages where the study strains clustered and lineages of global reference strains were identified and analyzed. Selection pressure analysis revealed that AA site seven in the Viral Protein 3 (VP3) genome segment was under positive selection. This site occurs in the region of intrinsic disorder in the VP3 protein, and Zambian G2P[4] strains could potentially be utilizing this intrinsically disordered region to survive immune pressure. The Zambian G2P[4] strains from 2012 to 2016 comprised the G2P[4] strains that have been circulating globally since the early 2000s, highlighting the epidemiological fitness of these contemporary G2P[4] strains. Continuous whole-genome surveillance of G2P[4] strains remains imperative to understand their evolution during the post-vaccination period.
AB - The G2P[4] genotype is among the rotavirus strains that circulate commonly in humans. Several countries have reported its immediate upsurge after the introduction of rotavirus vaccination, raising concern about sub-optimal vaccine effectiveness against this genotype in the long term. This study aimed to gain insight into the evolution of post-vaccine Zambian G2P[4] group A rotavirus (RVA) strains and their overall genetic make-up by analysis of sequence alignments at the amino acid (AA) level. Twenty-nine Zambian G2P[4] rotavirus strains were subjected to whole-genome sequencing using the Illumina MiSeq® platform. All the strains exhibited the typical DS-1-like genotype constellation, and the nucleotide sequences of the 11 genome segments showed high nucleotide similarities (>97%). Phylogenetic analyses together with representative global G2P[4] RVA showed that Zambian strains clustered into human lineages IV (for VP2, VP4, VP7, NSP1, and NSP5), V (for VP1, VP3, VP6, NSP2, and NSP3), and XXIII (for NSP4). The AA differences between the lineages where the study strains clustered and lineages of global reference strains were identified and analyzed. Selection pressure analysis revealed that AA site seven in the Viral Protein 3 (VP3) genome segment was under positive selection. This site occurs in the region of intrinsic disorder in the VP3 protein, and Zambian G2P[4] strains could potentially be utilizing this intrinsically disordered region to survive immune pressure. The Zambian G2P[4] strains from 2012 to 2016 comprised the G2P[4] strains that have been circulating globally since the early 2000s, highlighting the epidemiological fitness of these contemporary G2P[4] strains. Continuous whole-genome surveillance of G2P[4] strains remains imperative to understand their evolution during the post-vaccination period.
KW - DS-1-like genotype constellation
KW - G2P[4]
KW - Zambia
KW - rotavirus
KW - whole-genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85149227909&partnerID=8YFLogxK
U2 - 10.3390/v15020501
DO - 10.3390/v15020501
M3 - Article
C2 - 36851715
AN - SCOPUS:85149227909
SN - 1999-4915
VL - 15
JO - Viruses
JF - Viruses
IS - 2
M1 - 501
ER -
