An increasing prevalence of recombinant GII norovirus in pediatric patients with diarrhea during 2010–2013 in Chinaby Qing-Bin Lu, Dou-Dou Huang, Jin Zhao, Hong-Yu Wang, Xiao-Ai Zhang, Hong-Mei Xu, Fen Qu, Wei Liu, Wu-Chun Cao

Infection, Genetics and Evolution

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13 G 4 iQ1 5 6 7 Q2 -Y 8 9 10 d Ep 11 12 13 14 15 1 7 a r t i c l e i n f o 18 Article history: 19 20 21 22 23 24 25 26 27 28 29 3 0 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 into three open reading frames (ORFs), labeled ORF1, 2, and 3, that 59 60 61 62 63 64 65F1) and structural 66eages, providing 67lly novel 68diversity f 69together with its low infectious dose, lack of long-term pro 70immunity, and high stability in natural environment, has 71norovirus gastroenteritis a major public health concern worldwide, 72however, for which there is no available antiviral agent or effective 73vaccine (Hutson et al., 2004; Tan and Jiang, 2010). 74Noroviruses are classified into five genogroups based upon the 75phylogenetic analysis of the VP1 gene, among which genogroups 76I (GI) and II (GII) are most commonly associated with human infec77tions. To date, GII noroviruses have been further subdivided into 31 ⇑ Corresponding authors at: State Key Laboratory of Pathogen and Biosecurity,

Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai

District, Beijing 100071, PR China. Tel./fax: +86 1063896082.

E-mail addresses: qingbinlu@bjmu.edu.cn (Q.-B. Lu), 529443806@qq.com (D.-D. Huang), 545505784@qq.com (J. Zhao), 117935354@qq.com (H.-Y. Wang), babylovehopi@163.com (X.-A. Zhang), xuhongmwpx@yahoo.com (H.-M. Xu), qf302@163.com (F. Qu), lwbime@163.com (W. Liu), caowc@bmi.ac.cn (W.-C. Cao). 1 These authors contribute equally to this work.

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MEEGID 2216 No. of Pages 5, Model 5G 17 January 2015

Q1and possess a linear, single-stranded positive-sense RNA genome (Xi et al., 1990). This polyadenylated RNA genome contains approximately 7600 nucleotides (nt) packaged within a naked icosahedral 27–32-nm-diameter virion. The genome is organized as it facilitates the exchange of nonstructural (OR (ORF2-3) genes between different norovirus lin another mechanism for generating antigenica (Bull et al., 2007; Nayak et al., 2008). This highhttp://dx.doi.org/10.1016/j.meegid.2015.01.008 1567-1348/ 2015 Published by Elsevier B.V.

Please cite this article in press as: Lu, Q.-B., et al. An increasing prevalence of recombinant GII norovirus in pediatric patients with diarrhea during 2013 in China. Infect. Genet. Evol. (2015), http://dx.doi.org/10.1016/j.meegid.2015.01.008viruses eature, tective made 2015 Published by Elsevier B.V. 1. Introduction

Noroviruses are the primary cause of acute nonbacterial gastroenteritis in humans worldwide and are responsible for nearly half of gastroenteritis cases globally (Atmar and Estes, 2006; Glass et al., 2009). Noroviruses are members of the family Caliciviridae encode RNA-dependent RNA polymerase (RdRp), a major capsid protein VP1 and a small capsid protein VP2, respectively (Bull et al., 2005). In addition to accumulating point mutations associated with error-prone RNA replication, norovirus undergoes frequent homologous recombination, with breakpoints most often identified at the ORF1/2 overlap. This recombination is importantReceived 11 November 2014

Received in revised form 18 December 2014

Accepted 7 January 2015

Available online xxxx

Keywords:

Norovirus

Recombinant

Diarrhea

Children

Chinaa b s t r a c t

Noroviruses are the primary cause of acute nonbacterial gastroenteritis in humans and are responsible for nearly half of gastroenteritis cases globally. The norovirus strain variants have been circulating in underdeveloped regions in western China, where pediatric diarrhea acts as the major public health concern.

The study aims to identify the epidemic genotypes of norovirus and explore their genetic characteristics in Chongqing, China. By performing a hospital-based surveillance from 2010 to 2013, we identified a significant shift of the predominant Norovirus strains in recent 4 years in the studied area. The GII.4_Sydney_2012 and GII.12/GII.3 strains replaced GII.4_2006b and GII.4_NewOrleans_2009 to become the predominant genotypes, with the proportion of ORF1/ORF2 recombinants rising steadily from 2010 to 2013. A new GII.12/GII.3 variant that was seldom detected became a predominant genotype during the study course. Several distinct genotypes of norovirus, including GII.16/GII.2, GII.21/GII.3, GII.15 and

GII.6, were also detected. The rising circulation of recombination in Chongqing illustrated the significance of recombination, especially in the ORF1/ORF2 overlap region, in the evolution and epidemic of norovirus.

The epidemic of GII.12/GII.3 in Chongqing also serves as a reminder that prolonged surveillance is warranted for better prevention and control of norovirus infection.dChildren’s Hospital, Chongqing Medical University, Chongqing 400014, PR China e The PLA 302 hospital, Beijing 100039, PR ChinaAn increasing prevalence of recombinant patients with diarrhea during 2010–2013

Qing-Bin Lu a,1, Dou-Dou Huang b,c,1, Jin Zhao b, Hong

Fen Qu e, Wei Liu b,c,⇑, Wu-Chun Cao b,⇑ a School of Public Health, Peking University, Beijing 100191, PR China b State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology an cGraduate School of Anhui Medical University, Hefei 230032, PR ChinaII norovirus in pediatric n China u Wang b,c, Xiao-Ai Zhang b, Hong-Mei Xu d, idemiology, Beijing 100071, PR China le at ScienceDirect s and Evolution evier .com/locate /meegid2010– 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 ical University from January 2010 to December 2013. The acute 110 diarrhea was defined as three or more loose stools within a 24-h 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187while GII.12/GII.3 was found throughout the year (Fig. 3). The pro188 189 190 191 192 s an