Genetic Susceptibility to Norovirus GII.3 and GII.4 Infections in Chinese Pediatric Diarrheal Disease

Abstract

Background Noroviruses (NoVs) are a leading cause of viral diarrhea in young children. Secretor status has been confirmed to be linked with Norwalk virus (NoV GI.1) infection but there is limited information about whether secretor genotypes are associated with pediatric NoV epidemic strains in vivo. Methods In this study, fecal specimens and serum samples were collected from 124 hospitalized children with acute diarrhea in Xi'an, China. TaqMan real-time RT-PCR was used to detect NoV in fecal samples and NoV positive samples were further verified using conventional RT-PCR and sequenced. DNA was extracted from sera and TaqMan single nucleotide polymorphism genotyping assay was applied to determine FUT2 A385T polymorphism. Results Only NoV GII.3 and GII.4 genotypes were found in NoV positive samples and NoV were detected in 25% (15/60), 40.5% (17/42), and 9.1% (2/22) of children with homozygous secretor genotype (Se385Se385), heterozygous secretor genotype (Se385se385), and homozygous weak secretor genotype (se385se385), respectively. Children with secretor genotypes (Se385Se385 and Se385se385) were significantly (P < 0.05) more susceptible to combined NoV GII.3 and GII.4 infections than children with weak secretor genotype (se385se385). Conclusions These findings indicate that secretor positive is significantly associated with GII.3 and GII.4 infections in Chinese pediatric diarrheal children and weak secretor is not a complete protection of children from GII.3 and GII.4 infections.

Seroepidemiology of Norovirus GII.3 and GII.4 Infections in Children with Diarrhea in Xi'an, China

“…Blood group O had an increased and blood group B had a decreased risk of NoV infection (Hutson et al, 2002;Rockx et al, 2005). The study from our group indicated that NoV-specific IgG titers among children with homozygous and heterozygous secretor were higher than the titer of homozygous weak secretor children (Liu et al, 2014), suggesting that secretor status plays an important role in seroprevalence. In addition to these major factors, other factors such as age span, developing gut microflora, evolving immune system, and sex ratio (Peasey et al, 2004) may also impact NoV seroprevalence.…”

“…In the past decade, NoV GII.4 and GII.3 have been identified as the predominant genotypes in young children with nonbacterial acute diarrhea in China (Dai et al, 2004;Cheng et al, 2010;Hoa Tran et al, 2013). Our studies showed that GII.3 and GII.4 were the only NoV genotypes in hospitalized diarrheal children under 5 years in Xi'an, China (Zhang et al, 2011), and GII.3 and GII.4 infections in young children are significantly associated with host genetic susceptibility (Liu et al, 2014). The objective of this study was to investigate epidemiological information about NoV seroprevalence in diarrheal children in Xi'an, China through GII.3 and GII.4 VLPs expressed by the baculovirus expression system.…”

“…Subsequently, a 140-lL supernatant was removed and used for Norovirus RNA extraction using the QIAamp Viral RNA Mini Kit (Qiagen, Valencia, CA). Detailed methods for NoV RNA extraction, polymerase chain reaction (PCR) amplification, and genotyping has been described in our previous studies (Zhang et al, 2011;Liu et al, 2014). Based on previous results, a 2.3-kb cDNA fragment, which contains the VP1 region (NoV capsid protein) and the VP2 region encoding structural proteins of NoV GII.3 and NoV GII.4, was amplified by the primers shown in Table 1.…”

“…Serum and fecal specimens (used in previous studies [Zhang et al, 2011;Liu et al, 2014]) were collected from hospitalized children £ 5 years of age who were clinically diagnosed with acute gastroenteritis (defined as ‡ 3 loose or watery stools per day without blood and mucus) and whose clinical symptoms lasted < 2 weeks before admission to the Department of Digestive Diseases of Xi'an Children's Hospital between March 2009 and October 2012. Serum samples were collected once within 48 h of admission in the acute course of diarrhea.…”

No crucial amino acid changes in the predicted histo blood group antigen-binding sites of norovirus genotype GII.4 capsid between non-secretors and secretors origin might suggest an alternative route of infection or existence of coincidental molecules

“…According to Marionneau et al (2002), the virus binds to HBGAs on gastroduodenal epithelial cells of secretors, but not of non-secretors. Secretor-negative individuals are at much lower risk of infection with genotypes GI.1 (Lindesmith et al, 2003), GII.3 (Tan et al, 2008;Liu et al, 2014) and GII.4 (Thorven et al, 2005;Larsson et al, 2006;Kindberg et al, 2007). However, the relationship of secretor status to risk of infection with other genotypes is less clear.…”