Whole-Genome Analyses Identifies Multiple Reassortant Rotavirus Strains in Rwanda Post-Vaccine Introduction

Sebotsana Rasebotsa,Jason M Mwenda,M Jeffrey Mphahlele,Nonkululeko B Magagula,Milton T Mogotsi,Jeannine Uwimana,Martin M Nyaga,Leon Mutesa,Mapaseka L Seheri,Saheed Sabiu,Richard Mihigo,Kebareng Rakau

doi:10.3390/v13010095

Abstract

Children in low-and middle-income countries, including Rwanda, experience a greater burden of rotavirus disease relative to developed countries. Evolutionary mechanisms leading to multiple reassortant rotavirus strains have been documented over time which influence the diversity and evolutionary dynamics of novel rotaviruses. Comprehensive rotavirus whole-genome analysis was conducted on 158 rotavirus group A (RVA) samples collected pre- and post-vaccine introduction in children less than five years in Rwanda. Of these RVA positive samples, five strains with the genotype constellations G4P[4]-I1-R2-C2-M2-A2-N2-T1-E1-H2 (n = 1), G9P[4]-I1-R2-C2-M2-A1-N1-T1-E1-H1 (n = 1), G12P[8]-I1-R2-C2-M1-A1-N2-T1-E2-H3 (n = 2) and G12P[8]-I1-R1-C1-M1-A2-N2-T2-E1-H1 (n = 1), with double and triple gene reassortant rotavirus strains were identified. Phylogenetic analysis revealed a close relationship between the Rwandan strains and cognate human RVA strains as well as the RotaTeq® vaccine strains in the VP1, VP2, NSP2, NSP4 and NSP5 gene segments. Pairwise analyses revealed multiple differences in amino acid residues of the VP7 and VP4 antigenic regions of the RotaTeq® vaccine strain and representative Rwandan study strains. Although the impact of such amino acid changes on the effectiveness of rotavirus vaccines has not been fully explored, this analysis underlines the potential of rotavirus whole-genome analysis by enhancing knowledge and understanding of intergenogroup reassortant strains circulating in Rwanda post vaccine introduction.

Highlights

IntroductionGroup A rotaviruses (RVA) are the most common cause of severe virus-induced diarrhea in infants and children less than five years of age in both developed and developing countries, accounting for over 128,500 deaths globally in 2016, of which 104,733 occurred in sub-Saharan Africa [1]
In order to gain insight into the genetic variability among the study strains and their genetic relatedness with selected global reference rotavirus group A (RVA) strains, the full-genome sequences of 158 Rwandan samples sequenced from the pre- (2011) and post- (2012–2016) vaccination period were determined
The detection of five intergenogroup reassortant Rwandan rotavirus strains from the whole-genome analysis further emphasizes the ubiquitous nature and diversity of RVA strains in circulation

Summary

Introduction

Group A rotaviruses (RVA) are the most common cause of severe virus-induced diarrhea in infants and children less than five years of age in both developed and developing countries, accounting for over 128,500 deaths globally in 2016, of which 104,733 occurred in sub-Saharan Africa [1]. Children living in low-and middle-income countries have a higher disease burden due to poor living conditions, inadequate sanitation and limited supply of clean drinking water, among other factors [2,3]. Prior to the introduction of the vaccine RotaTeq® (RV5, Merck & Co. Inc., Kenilworth, NJ, USA) in Rwanda, approximately. 3500 RVA related mortality was reported in children annually, accounting for 8.8% of all mortality rate in children less than five years of age [4]. RotaTeq® was introduced into the Rwandan National Immunization Program in May 2012 with a vaccine coverage of

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