Genome-Wide Evolutionary Analyses of G1P[8] Strains Isolated Before and After Rotavirus Vaccine Introduction

Abstract

Rotaviruses are the most important etiological agent of acute gastroenteritis in young children worldwide. Among the first countries to introduce rotavirus vaccines into their national immunization programs were Belgium (November 2006) and Australia (July 2007). Surveillance programs in Belgium (since 1999) and Australia (since 1989) offer the opportunity to perform a detailed comparison of rotavirus strains circulating pre- and postvaccine introduction. G1P[8] rotaviruses are the most prominent genotype in humans, and a total of 157 G1P[8] rotaviruses isolated between 1999 and 2011 were selected from Belgium and Australia and their complete genomes were sequenced. Phylogenetic analysis showed evidence of frequent reassortment among Belgian and Australian G1P[8] rotaviruses. Although many different phylogenetic subclusters were present before and after vaccine introduction, some unique clusters were only identified after vaccine introduction, which could be due to natural fluctuation or the first signs of vaccine-driven evolution. The times to the most recent common ancestors for the Belgian and Australian G1P[8] rotaviruses ranged from 1846 to 1955 depending on the gene segment, with VP7 and NSP4 resulting in the most recent estimates. We found no evidence that rotavirus population size was affected after vaccine introduction and only six amino acid sites in VP2, VP3, VP7, and NSP1 were identified to be under positive selective pressure. Continued surveillance of G1P[8] strains is needed to determine long-term effects of vaccine introductions, particularly now rotavirus vaccines are implemented in the national immunization programs of an increasing number of countries worldwide.

Comparative analysis of the Rotarix™ vaccine strain and G1P[8] rotaviruses detected before and after vaccine introduction in Belgium

“…Previously, we have shown in a large comparative study comprising Belgian and Australian RVA strains that gene segments probably have distinct evolutionary histories and that unique phylogenetic subclusters were present after vaccine introduction (Zeller et al, 2015). Here we show by using the same G1P[8] sample collection that depending on the gene segment, substantial differences exist in comparison with the Rotarix™ vaccine strain and that non-Rotarix™ clusters were more prevalent after vaccine introduction.…”

“…For each sample approximately 50 mg of collected feces was resuspended in 500 µl PBS and viral RNA was subsequently extracted with the Qiagen Viral RNA minikit (Qiagen) according to the manufacturer’s instructions. In total 100 µl of viral RNA was sent to the J. Craig Venter Institute for RT-PCR and sequencing in a high-throughput fashion as described previously (McDonald et al, 2009; Zeller et al, 2015). A Rotarix™ G1P[8] vaccine strain was commercially obtained in Belgium to compare the vaccine strain with circulating RVAs in Belgium, and reconstituted according to manufacturer’s recommendations (lot number: A41CB052A).…”

“…However, none of these studies specifically investigated the effect of vaccine introduction on the intra-genotype dynamics of commonly circulating Wa-like strains. Previously, we have reported the G1P[8] strain diversity in Belgium and Australia, and showed the existence of unique subclusters that were present only after vaccine introduction (Zeller et al, 2015). In this study we investigate 70 Belgian G1P[8] strains in relationship with the Rotarix™ vaccine.…”

Epidemiology of rotavirus A diarrhea in Chókwè, Southern Mozambique, from February to September, 2011

“…Similar results were reported by Imbert‐Marcille et al [] showing a wide circulation of P[8]‐3 associated with different G genotypes in 62 patients with diarrhea in France during 2010–2012. The MOZ21162 grouped inside the P[8]‐4 lineage, a relatively recent lineage of P[8] reported in different parts of Europe, Africa, and Asia [Zade et al, ; Tamura et al, ; Zhirakovskaia et al, ; Zeller et al, ]. Since information on P[8]‐4 sequence is rather limited in current available literature the effectiveness of the two RVA vaccines available worldwide against this lineage is not known.…”

Distinguishing the genotype 1 genes and proteins of human Wa-like rotaviruses vs. porcine rotaviruses

“…2A) included those that were isolated during the years of 2004–2011 from diarrheic children at various geographical locations: Thailand (strains CU938-BK, CU747-KK, and CU460-KK), Africa (strains MRC-DPRU1424, MRC-DPRU1723, and MRC-DPRU1262), Belgium (strains BE00030, BE00043, BE00055, B4633, and B3458), the United States (strains 2008747100, 2008747288, 2007719720, VU08-09-20, VU06-07-21, VU06-07-32, VU05-06-2, and VU05-06-47), Australia (strains CK00100, CK00088, CK00034, and CK00005), China (strains R588 and Y128), Italy (strains JES11 and AV21), Germany (strains GER126-08 and GER172-08), India (strains 61060 and 6361), and Paraguay (strains 954SR and 1638SR) (Arora and Chitambar, 2011; Ianiro et al, 2013; Matthijnssens et al, 2008; McDonald et al, 2012; Nyaga et al, 2013; Pietsch and Liebert, 2009; Rahman et al, 2007; Shintani et al, 2012; Theamboonlers et al, 2014; Zeller et al, 2015). …”