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The emergence of the novel GII.17 Kawasaki 2014 norovirus variant raising the interest of the public, has replaced GII.4 as the predominant cause of noroviruses outbreaks in East Asia during 2014–2015. Antigenic variation of the capsid protein is considered as one of the key mechanisms of norovirus evolution. In this study, we screened a panel of GII.17 mutants. First, we produced norovirus P proteins using cell-free protein synthesis (CFPS) system, comparing the results to pure proteins expressed in a cell-based system. Next, we determined the binding capability of specific monoclonal antibody (mAb) 2D11 using a unique set of wild-type GII.17 strains. Results of the EIA involving a panel of mutant cell-free proteins indicated that Q298 was the key residue within loop 1. These data highlighted the essential residues in the linear antibody binding characteristics of novel GII.17. Furthermore, it supported the CFPS as a promising tool for rapidly screening mutants via the scalable expression of norovirus P proteins. [ABSTRACT FROM AUTHOR]

• ddPCR is a helpful technology for plasma analysis to detect T790M mutation. • Plasma analysis is high specificity enough for screening T790M mutation. • ctDNA and cfDNA have the same performance. T790M mutation was a primary lead cause in the acquired resistance to EGFR-TKIs confirmed in earlier studies. Since the shortcomings of tumor tissue detection are well known, the liquid biopsy is more appropriate to track T790M status. We assessed the accuracy and clinical significance of the droplet digital PCR (ddPCR) detection of T790M mutation in plasma. We retrieved PubMed, Embase, Cochrane, and Web of science with no limitation of language and publication year. Summary sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio of detection of EGFR T790M status were calculated from extracted data from included articles. The summary receiver operating curve (SROC), diagnostic odds ratio (DOR), and the area under the summary receiver operating curve (AUC) was used to assess the overall diagnostic accuracy. I2 and meta-regression were used to evaluate heterogeneity and the source of heterogeneity, respectively. We identified 15 studies in the total search of 1364 reports, including 427 paired tissue and plasma samples. The pooled sensitivity and the pooled specificity were 0.68 (95% CI 0.61–0.75) and 0.85 (95% CI 0.75–0.91) by the bivariate model, respectively. The AUC and the pooled DOR were 0.78 (95% CI 0.74–0.81) and 12 (95% CI 7–22), respectively. None of the cofactors could account for the heterogeneity. The plasma analysis is of a promising performance to screen EGFR-T790M mutation status by ddPCR. [ABSTRACT FROM AUTHOR]

Dengue virus infection (DEN) is one of the most prevalent arbovirus diseases in the tropical and subtropical areas. Some human leukocyte antigen (HLA) alleles have been reported to be a protective or risk factor to DEN. Due to the limited sample sizes and regional limitations, the results of individual studies were various. This meta-analysis aimed at investigating the relationship between HLA alleles and dengue disease. Relevant studies of the relationship between HLA and dengue disease were searched through PubMed, Embase, Web of science, and Cochrane databases. Subgroups according to ethnicity or sub-alleles and sensitivity analysis were used to explore the potential source of heterogeneity, which was performed to confirm the findings. The relationships between HLA and dengue disease were defined by odds ratios (ORs) with a 95% confidence interval (CI). Fourteen studies were finally confirmed. Results indicated that A*0203 (OR = 2.19, 95% CI = 1.30–3.69) and A*24 in the Asian group (OR = 1.44, 95% CI = 1.21–1.71) were positively associated with an increased risk of DEN when compared with normal controls. A*33 (OR = 0.49, 95% CI = 0.34–0.69) in Southeast Asia was negatively associated with DEN when compared with normal controls, suggesting a protective role against DEN. In addition, DRB1*11 (OR = 4.10, 95% CI = 1.23–13.69) was positively associated with severe dengue (SD) when compared with dengue fever, whereas DRB1*03 (OR = 0.48, 95% CI = 0.28–0.82) and DRB1*09 (OR = 0.73, 95% CI = 0.55–0.96) were negatively associated with SD when compared with normal controls. The meta-analysis confirmed that HLA-A*0203, A*24, A*33, DRB1*03, DRB1*09, and DRB1*11 have significantly affected dengue disease, and the associations are related to race and regions. [ABSTRACT FROM AUTHOR]

Norovirus is a major cause of acute gastroenteritis worldwide. Like the major capsid protein (VP1), the minor capsid protein (VP2) also contains a hypervariable domain. Generally, a hypervariable domain is functionally driven. However, many functions of VP2 remain unknown and worth exploring. Without sufficient sequences and an available crystallographic model, it is difficult to explore VP2's mysteries. As a helper of stabilizing and coordinating the formation of virus-like particles (VLPs), we asked whether VP2 interacted with the major capsid protein (VP1) in GII.17 and if so, what the key interaction residues were. Here, we reported cross-interaction among four strains represented four clusters of GII.17, and the VP1 interaction domain of VP2 (174-179aa) was found. However, the VP1 interaction domain of VP2 was not universal in different clusters of GII.17. VP2 might evolve in a different pattern from VP1. Additionally, in contrast to previous reports, we found that VP2 localized in the cytoplasm. More possibilities of VP2 should be further explored. • Unlike the covariation of GII.4, cross-interactions are confirmed in four clusters of GII.17. • In the epidemic GII.17 strain, residues of 174–179 of VP2 are responsible for interacting with VP1. • The evolutionary pattern of VP2 might be different from VP1 and other possibilities of VP2 should be explored. [ABSTRACT FROM AUTHOR]

The worldwide response towards the acute gastroenteritis epidemic was well known, but the absence of an updated systematic review of global norovirus epidemiology in cases of gastroenteritis existed. We aimed to conduct and update a systematic review and meta-analysis of studies assessing norovirus prevalence among gastroenteritis patients worldwide. Four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched for epidemiological papers from 2014 to 2021 which applied the PCR method to access the prevalence of norovirus in acute gastroenteritis patients more than a full year. Statistical analysis was conducted using R-4.0.0 software. A total of 405 records with 842, 926 cases were included. The pooled prevalence of norovirus was 16% (95%CI 15, 17). Children under 5 years old were at a higher risk with norovirus. A higher prevalence was seen in South America (22%, 95% CI 18, 27), while other continents showed a similar result with the overall prevalence of norovirus. No association was found between national income level and norovirus prevalence. A gradient of decreasing prevalence was noticed from community (20%, 95% CI 16, 24) to outpatients (18%, 95% CI 16, 20) to hospital setting (included both in- and outpatients, 17%, 95% CI 16, 19) to inpatients (15%, 95% CI 13, 17). Norovirus were associated with 16% acute gastroenteritis globally. To fully understand the prevalence of norovirus worldwide, the continual surveillance of norovirus epidemics was required. • The pooled global prevalence of norovirus among acute gastroenteritis was 16% over the last 20 years. • The infection rate stayed the same compared to the last decade. • Norovirus should be included in continuous surveillance worldwide, especially in low-incoming countries. [ABSTRACT FROM AUTHOR]

Norovirus is responsible for the viral gastroenteritis burden worldwide. Histo-blood type antigens (HBGAs) are the only well-known factor regarding their effect on the pathogenesis of norovirus. Here, we performed the study to further investigate the association of the ABO blood group with norovirus susceptibility. All relevant studies were retrieved from PubMed, Embase, Web of Science, and Cochrane Library databases and the associations of ABO blood groups with norovirus were assessed. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated from extracted data. I 2 statistics, sensitivity analysis, and publication bias were used to confirm the findings. Subgroup analyses were performed for genotypes, publication years, development degree of the countries, and age if heterogeneity was recorded. Seventeen articles covering 2304 participants were included. The overall analysis of the studies showed similar ORs of norovirus infection among individuals with blood type A (OR = 0.90, 95%CI = 0.71–1.14, P = 0.37) and blood type B (OR = 0.85, 95%CI = 0.66–1.12, P = 0.25) as compared to those controls. An increased odds of norovirus infection was found among individuals with blood type O (OR = 1.28, 95%CI = 1.03–1.59, P = 0.03), while the individuals with blood type AB (OR = 0.91, 95%CI = 0.60–1.39, P = 0.67) showed no correlation with norovirus infection. For blood type B and blood type AB, the results of subgroup analyses mirrored the observations above. The meta-analysis suggested that the blood type A, B and AB might not affect susceptibility to norovirus infection. However, blood type O appeared to be more susceptible to norovirus infection. • ABO blood groups are probably susceptibility factors of norovirus infection. • Blood type O is significantly associated with norovirus infection. • Blood types A, B, and AB have no correlation with norovirus infection. [ABSTRACT FROM AUTHOR]

Norovirus is a leading cause of viral gastroenteritis outbreaks worldwide. Histo-blood group antigens (HBGAs) are important host attachment factors in susceptibility to norovirus. In this study, the association of FUT2 gene, which participates in the biosynthesis of HBGAs, with norovirus infection has been investigated. All relevant studies on the associations of FUT2 gene with norovirus were retrieved from PubMed, Web of Science, Embase, and Cochrane Library databases. Odds ratios (ORs) and 95% confidence interval (CI) were used to analyze the extracted data. I 2 statistic, sensitivity analysis and publication bias analysis were used to confirm the findings. Subgroup analyses were performed for races, genotypes, development degree of the countries, publication years, age and setting when heterogeneity was recorded. Twenty studies including 4066 participants were included for the meta-analysis. This analysis showed that there is a significant association between FUT2 gene and norovirus infection (OR = 3.02, 95%CI = 2.00–4.55, P < 0.001). Additionally, the ORs of norovirus infection among Chinese (OR = 4.49, 95%CI = 2.37–8.50, P < 0.001) were higher than those among Caucasian (OR = 3.23, 95%CI = 2.20–4.74, P < 0.001). The meta-analysis suggested that FUT2 gene is associated with susceptibility to norovirus infection. • The association of non-sense mutation in FUT2 gene and norovirus infection was systematically evaluated. • Individuals with functional FUT2 gene were more vulnerable to norovirus infection. • The secretory status was significantly associated with the clinical symptoms of norovirus infection. [ABSTRACT FROM AUTHOR]

Noroviruses are the primary cause of gastroenteritis and foodborne diseases, affecting millions of individuals annually worldwide. Oysters are frequently associated with norovirus outbreaks. Hence, inexpensive and simple norovirus detection methods are important to detect and contain foodborne illness outbreaks. The objective of this study is to develop a high-efficient concentrated pretreatment method for reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) detection. Based on the existing ISO/TS 15216-2:2013 standard (ISO/TS 15216-2., 2013), four methods are compared for recovery of norovirus from spiked digestive tissue of oysters. A method is found to be the most efficient based on protease K method of increasing buffer volume and PEG precipitation method. The recovery rate and amplification efficiency approached 11.07 ± 0.09% and 124.12 ± 5.99%, respectively, being 7-fold that of the original ISO/TS 15216-2:2013 method. This method serves as a rapid (1.5h) sample concentration tool with a limit of detection as low as 7.05 × 103 copies. Thirty-eight oyster samples from an aquatic products market in Guangzhou are tested using this method, and noroviruses are detected in 13 samples. This method is an effective extension of the existing ISO/TS 15216-2:2013 standard and it is potentially applicable for detecting norovirus contamination in oysters. • PEG precipitation with proteinase K treatment was performed to detect NoV in independent oysters. • This method had a higher recovery rate than the standard ISO/TS 15216-2:2013 method. • This method had a better amplification efficiency upon RT-qPCR-based monitoring. [ABSTRACT FROM AUTHOR]