Understanding the relationship between norovirus diversity and immunity

Human noroviruses are the most common viral cause of acute gastroenteritis worldwide. Currently, there are no approved vaccines or specific therapeutics to treat the disease. Some obstacles delaying the development of a norovirus vaccine are: (i) the extreme diversity presented by noroviruses; (ii) our incomplete understanding of immunity to noroviruses; and (iii) the lack of a robust cell culture system or animal model for human noroviruses. Recent advances in in vitro cultivation of norovirus, novel approaches applied to viral genomics and immunity, and completion of vaccine trials and birth cohort studies have provided new information toward a better understanding of norovirus immunity. Here, we will discuss the complex relationship between norovirus diversity and correlates of protection for human noroviruses, and how this information could be used to guide the development of cross-protective vaccines

Population Genomics of GII.4 Noroviruses Reveal Complex Diversification and New Antigenic Sites Involved in the Emergence of Pandemic Strains

Noroviruses are an important cause of viral gastroenteritis around the world. An obstacle delaying the development of norovirus vaccines is inadequate understanding of the role of norovirus diversity in immunity. Using a population genomics approach, we identified new residues on the viral capsid protein (VP1) from GII.4 noroviruses, the predominant genotype, that appear to be involved in the emergence and antigenic topology of GII.4 variants. Careful monitoring of the substitutions in those residues involved in the diversification and emergence of new viruses could help in the early detection of future novel variants with pandemic potential. Therefore, this novel information on the antigenic diversification could facilitate GII.4 norovirus vaccine design.GII.4 noroviruses are a major cause of acute gastroenteritis. Their dominance has been partially explained by the continuous emergence of antigenically distinct variants. To gain insights into the mechanisms of viral emergence and population dynamics of GII.4 noroviruses, we performed large-scale genomics, structural, and mutational analyses of the viral capsid protein (VP1). GII.4 noroviruses exhibited a periodic replacement of predominant variants with accumulation of amino acid substitutions. Genomic analyses revealed (i) a large proportion (87%) of conserved residues; (ii) variable residues that map on the previously determined antigenic sites; and (iii) variable residues that map outside the antigenic sites. Residues in the third pattern category formed motifs on the surface of VP1, which suggested extensions of previously predicted and new uncharacterized antigenic sites. The role of two motifs (C and G) in the antigenic makeup of the GII.4 capsid protein was confirmed with monoclonal antibodies and carbohydrate blocking assays. Amino acid profiles from antigenic sites (A, C, D, E, and G) correlated with the circulation patterns of GII.4 variants, with three of them (A, C, and G) containing residues (352, 357, 368, and 378) linked with the diversifying selective pressure on the emergence of new GII.4 variants. Notably, the emergence of each variant was followed by stochastic diversification with minimal changes that did not progress toward the next variant. This report provides a methodological framework for antigenic characterization of viruses and expands our understanding of the dynamics of GII.4 noroviruses and could facilitate the design of cross-reactive vaccines

Phylogenetic Analyses Suggest that Factors Other Than the Capsid Protein Play a Role in the Epidemic Potential of GII.2 Norovirus

In this Article, Professor Clark addresses the legal issues surrounding the use of testers-individuals who deliberately apply for employment to detect sex and race discrimination. He surveys three theoretical justifications for granting standing to organizations that run testing programs. Professor Clark then responds to a previous article by Professor Yelnosky, disputing some of his conclusions. Professor Clark indicates that testing is just as necessary in higher-level employment as lower-level employment; shows that testers can obtain meaningful relief from the courts; analyzes the impact of the 1991 Civil Rights Act amendments; and encourages Congress to authorize the EEOC to run tester programs that are exempt from laws which prohibit misrepresentation of applicant credentials

Distribution and box-and-whisker plots of Cq values from qPCR targeting the norovirus GI and GII.

<p>The assays were conducted with (a) wastewater samples and (b) stool samples. The box indicates the median and the quartiles. The whiskers are drawn to the furthest points within the 1.5-times interquartile range from the box. Plots at Cq = 45 and 50 show positive but not quantifiable samples (original Cq > 40) and negative samples, respectively.</p

El Compostelano : diario independiente: Ano XXVI Número 7716 - 1945 novembro 1

Numeración errónea en el original

Number of positive/negative samples and the corresponding positive rates for each assay using wastewater or stool samples.

<p>Number of positive/negative samples and the corresponding positive rates for each assay using wastewater or stool samples.</p