Interaction between norovirus and Histo-Blood Group Antigens: A key to understanding virus transmission and inactivation through treatments?

Human noroviruses (HuNoVs) are a main cause of acute gastroenteritis worldwide. They are frequently involved in foodborne and waterborne outbreaks. Environmental transmission of the virus depends on two main factors: the ability of viral particles to remain infectious and their adhesion capacity onto different surfaces. Until recently, adhesion of viral particles to food matrices was mainly investigated by considering non-specific interactions (e.g. electrostatic, hydrophobic) and there was only limited information about infectious HuNoVs because of the absence of a reliable in vitro HuNoV cultivation system. Many HuNoV strains have now been described as having specific binding interactions with human Histo-Blood Group Antigens (HBGAs) and non-HBGA ligands found in food and the environment. Relevant approaches to the in vitro replication of HuNoVs were also proposed recently. On the basis of the available literature data, this review discusses the opportunities to use this new knowledge to obtain a better understanding of HuNoV transmission to human populations and better evaluate the hazard posed by HuNoVs in foodstuffs and the environment.

Transmission of hepatitis E virus by water: An issue still pending in industrialized countries.

Hepatitis E virus (HEV) is an enteric virus divided into eight genotypes. Genotype 1 (G1) and G2 are specific to humans; G3, G4 and G7 are zoonotic genotypes infecting humans and animals. Transmission to humans through water has been demonstrated for G1 and G2, mainly in developing countries, but is only suspected for the zoonotic genotypes. Thus, the water-related HEV hazard may be due to human and animal faeces. The high HEV genetic variability allows considering the presence in wastewater of not only different genotypes, but also quasispecies adding even greater diversity. Moreover, recent studies have demonstrated that HEV particles may be either quasi-enveloped or non-enveloped, potentially implying differential viral behaviours in the environment. The presence of HEV has been demonstrated at the different stages of the water cycle all over the world, especially for HEV G3 in Europe and the USA. Concerning HEV survival in water, the virus does not have higher resistance to inactivating factors (heat, UV, chlorine, physical removal), compared to viral indicators (MS2 phage) or other highly resistant enteric viruses (Hepatitis A virus). But the studies did not take into account genetic (genogroups, quasispecies) or structural (quasi- or non-enveloped forms) HEV variability. Viral variability could indeed modify HEV persistence in water by influencing its interaction with the environment, its infectivity and its pathogenicity, and subsequently its transmission by water. The cell culture methods used to study HEV survival still have drawbacks (challenging virus cultivation, time consuming, lack of sensitivity). As explained in the present review, the issue of HEV transmission to humans through water is similar to that of other enteric viruses because of their similar or lower survival. HEV transmission to animals through water and how the virus variability affects its survival and transmission remain to be investigated.

Molecular features of Hepatitis E Virus circulation in environmental and human samples.

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is emerging but its circulation between humans and the environment remains misunderstood. HEV ORF2 gene encodes the capsid playing a key role in viral interactions with surfaces, ORF3 products are involved in the viral cycle. Our aim was to study the molecular characteristics of ORF2 and ORF3 which could favor HEV fitness in patients and the environment. STUDY DESIGN: Samples from 69 patients with hepatitis (blood/stools), 20 urban wastewaters, 20 effluents of a pig slaughterhouse, 22 farm pigs (stools), 20 wild boars (liver/stools) were collected in North-Eastern France. HEV strains were analyzed by direct sequencing within the ORF2 M region, of ORF2/ORF3, for phylogeny and physicochemical prediction and for ORF2 by ultra-deep sequencing. RESULTS: The results showed frequent HEV-positive samples: 9.1% of the patient bloods, 23.1% of their stools; 25.0% of wastewaters, 75.0% for the slaughterhouse, 10.0% of the boar livers, 5.3% of their stools. The strains were classified as HEV genotype 3. In ORF2, HEV highlighted one homogeneous major viral variant within quasispecies and a decrease in predicted antigenicity for two minor mutations (D442G, V402A). A cysteine signature at position 81 in ORF3 was observed in the boars. CONCLUSIONS: HEV RNA genotype 3 was detected in patients and in animals, in a slaughterhouse effluent and in wastewater. Moreover, the low variability of amino acids in the ORF2 M region and molecular features in ORF2 and ORF3 suggested that HEV strains could be advantageous for key properties.

[Sephadex G 100- Separation of the mucicrinic and the mucimitiginic factors from an extract of duodenal mucosa (author's transl)]. / Séparation sur séphadex G 100 de facteurs mucicriniques et mucimitiginiques à partir d'un extrait de muqueuse duodénale

The mucicrin stimulating the hexosamine gastrointestinal secretion and extracted form porcine duodenum, was concentrated in the zone 7 using sephadex G 100. The molecular weight of 4000-5000 corresponds to this zone. An opposite activity was detected in zone 3. The factor from digestive mucous origin being able to diminish the hexosamine gastric secretion and not influencing the arterial pressure was called mucimitigin. The molecular weight of about 35000 corresponds to this factor.