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, 2014, 196169

Genetic Diversity and Distribution of Human Norovirus in China (1999-2011)

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Genetic Diversity and Distribution of Human Norovirus in China (1999-2011)

Yongxin Yu et al. Biomed Res Int.

Abstract

Noroviruses (NoVs) are a leading cause of epidemic and sporadic acute gastroenteritis worldwide. However, the genetic diversity and geographical distribution of NoV isolates from China have not been well described thus far. In this study, all NoV sequences obtained in China from 1999 to 2011 (n = 983), both partial and complete genomes, were downloaded from GenBank. Genotyping and phylogenetic and recombination analyses were performed in order to gain a better understanding of the distribution and genetic diversity of NoVs in China. The results indicated that approximately 90% of NoV sequences were obtained from the coastal regions of China, and most of the NoV sequences from distinct geographical regions appeared to be closely related. GII.4 was the most prevalent genotype, accounting for 64.4% of all genotypes, followed by GII.12 (13.9%) and GII.3 (7.0%). Over the last decade, the GII.4 variants were dominated by successive circulation of GII.4/2002, GII.4/2004, GII.4/2006b, and GII.4/2008, with GII.4/2006b continuing to date. A relatively high frequency of NoV intergenotype recombinants was identified. The most common ORF1/ORF2 intergenotype recombinant was GII.12/GII.4 (n = 11), and the relative frequency was up to 30% among all the recombinant strains (n = 36). These findings may aid in the evaluation and implementation of appropriate measures for monitoring NoV infectious diseases in China.

Figures

Figure 1
Figure 1
Genome map of norovirus (NoV; X86557). The NoV genome is composed of 3 open reading frames (ORFs). ORF1 (~5 kb) encodes the nonstructural proteins of an NTPase, 3C-like protease, and RNA-dependent RNA polymerase (RdRp). ORF2 is 1.8 kb in length and encodes the 57 kDa major structural capsid protein of viral protein 1 (VP1). VP1 is divided into the shell domain (S) and the protruding domain (P). The P domain contains two subdomains, known as P1 and P2. The regions of A, B, C, D, and E on NoV genome are used for genotyping. ORF3 encodes a minor structural protein VP2.
Figure 2
Figure 2
Diversity of NoV genotypes between 1999 and 2011 in China. (a) Genogroups of GI, GII and recombination (Re). (b) Genogroup I of GI.1, GI.2, GI.3, GI.4, GI.5, GI.6, GI.7, GI.8, and GI.b. (c) Genogroup II of GII.3, GII.4, GII.12, GII.b, and others (includes GII.2, GII.5, GII.6, GII.7, GII.8, GII.13, GII.14, GII.15, GII.16, GII.20, GII.21, and GII.a).
Figure 3
Figure 3
Distribution of NoV GII.4 variants based on ORF1 (a) and ORF2 (b). NA indicates the GII.4 sequences could not be assigned to any known variants.
Figure 4
Figure 4
Phylogenetic analysis of GII.4 NoV sequences from China. Two rooted phylogenetic trees were reconstructed using partial ORF1 (1029 nt) (a) and ORF2 (811 nt) (b) nucleotide sequences. GII.1 (JN797508) and GII.20 (AB542917) were used as the outgroups in (a) and (b), respectively. The trees were generated using the maximum-likelihood method. Bootstrap values above 70%, estimated with 1000 pseudoreplicate data sets, are indicated at each node. The distance scale represents the number of nucleotide substitutions per position. The variant clusters are highlighted, and the NoV GII.4 sequences from China are indicated with a diamond. The reference sequences were retrieved from the NCBI database. The subtree of the Den Haag 2006b cluster in (b) includes 47 representative sequences.
Figure 5
Figure 5
Geographical distribution of NoVs in China. (a) Sequence distribution map. The color-coding of each region is as follows: North China district (blue) includes Hebei, Shanxi, Beijing, and Tianjin; South China district (green) includes Guangdong, Guangxi, Hainan, and Hong Kong; East China district (red) includes Anhui, Shandong, Henan, Shanghai, Jiangsu, Zhejiang, and Fujian; North-East China district (purple) includes Jilin and Liaoning; West China district (yellow) includes Gansu, Xinjiang, Shanxi, Sichuan, Chongqing, Guizhou, and Yunnan. (b) Genotype distribution.
Figure 6
Figure 6
Phylogenetic recombination analyses of NoV sequences from China. Two unrooted phylogenetic trees were reconstructed using partial ORF1 (231 nt) (a) and ORF2 (259 nt) (b) nucleotide sequences. The trees were reconstructed using the maximum-likelihood method. Bootstrap values above 70%, estimated with 1000 pseudoreplicate data sets, are indicated at each node. The distance scale represents the number of nucleotide substitutions per position. The various genotypes are highlighted, and the recombination sequences from China are indicated with a diamond. The reference sequences were retrieved from the NCBI database.

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