Inhibition of cellular protein secretion by norwalk virus nonstructural protein p22 requires a mimic of an endoplasmic reticulum export signal.

Protein trafficking between the endoplasmic reticulum (ER) and Golgi apparatus is central to cellular homeostasis. ER export signals are utilized by a subset of proteins to rapidly exit the ER by direct uptake into COPII vesicles for transport to the Golgi. Norwalk virus nonstructural protein p22 contains a YXΦESDG motif that mimics a di-acidic ER export signal in both sequence and function. However, unlike normal ER export signals, the ER export signal mimic of p22 is necessary for apparent inhibition of normal COPII vesicle trafficking, which leads to Golgi disassembly and antagonism of Golgi-dependent cellular protein secretion. This is the first reported function for p22. Disassembly of the Golgi apparatus was also observed in cells replicating Norwalk virus, which may contribute to pathogenesis by interfering with cellular processes that are dependent on an intact secretory pathway. These results indicate that the ER export signal mimic is critical to the antagonistic function of p22, shown herein to be a novel antagonist of ER/Golgi trafficking. This unique and well-conserved human norovirus motif is therefore an appealing target for antiviral drug development

Vesivirus 2117 capsids more closely resemble sapovirus and lagovirus particles than other known vesivirus structures

Vesivirus 2117 is an adventitious agent that in 2009, was identified as a contaminant of CHO cells propagated in bioreactors at a pharmaceutical manufacturing plant belonging to Genzyme. The consequent interruption in supply of Fabrazyme and Cerezyme (drugs used to treat Fabry and Gaucher disease respectively), caused significant economic losses. Vesivirus 2117 is a member of the Caliciviridae; a family of small icosahedral viruses encoding a positive sense RNA genome. We have used cryo-electron microscopy and three dimensional image reconstruction to calculate a structure of vesivirus 2117 virus like particles as well as feline calicivirus and a chimeric sapovirus. We present a structural comparison of several members of the Caliciviridae, showing that the distal P domain of vesivirus 2117 is morphologically distinct from that seen in other known vesivirus structures. Furthermore, at intermediate resolutions we found a high level of structural similarity between vesivirus 2117 and Caliciviridae from other genera, such as sapovirus and rabbit haemorrhagic disease virus. Phylogenetic analysis confirms vesivirus 2117 as a vesivirus closely related to canine vesiviruses. We postulate that morphological differences in virion structure seen between vesivirus clades may reflect differences in receptor usage

Emerging and Re-Emerging Zoonoses of Dogs and Cats.

Since the middle of the 20th century, pets are more frequently considered as "family members" within households. However, cats and dogs still can be a source of human infection by various zoonotic pathogens. Among emerging or re-emerging zoonoses, viral diseases, such as rabies (mainly from dog pet trade or travel abroad), but also feline cowpox and newly recognized noroviruses or rotaviruses or influenza viruses can sicken our pets and be transmitted to humans. Bacterial zoonoses include bacteria transmitted by bites or scratches, such as pasteurellosis or cat scratch disease, leading to severe clinical manifestations in people because of their age or immune status and also because of our closeness, not to say intimacy, with our pets. Cutaneous contamination with methicillin-resistant Staphylococcus aureus, Leptospira spp., and/or aerosolization of bacteria causing tuberculosis or kennel cough are also emerging/re-emerging pathogens that can be transmitted by our pets, as well as gastro-intestinal pathogens such as Salmonella or Campylobacter. Parasitic and fungal pathogens, such as echinococcosis, leishmaniasis, onchocercosis, or sporotrichosis, are also re-emerging or emerging pet related zoonoses. Common sense and good personal and pet hygiene are the key elements to prevent such a risk of zoonotic infection

Norovirus Infection and Disease in an Ecuadorian Birth Cohort: Association of Certain Norovirus Genotypes With Host FUT2 Secretor Status.

BACKGROUND: Although norovirus is the most common cause of gastroenteritis, there are few data on the community incidence of infection/disease or the patterns of acquired immunity or innate resistance to norovirus. METHODS: We followed a community-based birth cohort of 194 children in Ecuador with the aim to estimate (1) the incidence of norovirus gastroenteritis from birth to age 3 years, (2) the protective effect of norovirus infection against subsequent infection/disease, and (3) the association of infection and disease with FUT2 secretor status. RESULTS: Over the 3-year period, we detected a mean of 2.26 diarrheal episodes per child (range, 0-12 episodes). Norovirus was detected in 260 samples (18%) but was not found more frequently in diarrheal samples (79 of 438 [18%]), compared with diarrhea-free samples (181 of 1016 [18%]; P = .919). A total of 66% of children had at least 1 norovirus infection during the first 3 years of life, and 40% of children had 2 infections. Previous norovirus infections were not associated with the risk of subsequent infection. All genogroup II, genotype 4 (GII.4) infections were among secretor-positive children (P < .001), but higher rates of non-GII.4 infections were found in secretor-negative children (relative risk, 0.56; P = .029). CONCLUSIONS: GII.4 infections were uniquely detected in secretor-positive children, while non-GII.4 infections were more often found in secretor-negative children

Norovirus transfer between foods and food contact materials

Human infective noroviruses (NoVs) are a worldwide leading cause of foodborne illness and are frequently spread via infected food handlers preparing and manipulating food products such as deli sandwiches. The objective of the current study was to determine the efficiencies whereby NoV could be transferred between surfaces associated with the preparation of manually prepared foods such as deli sandwiches. Nonfood surfaces included gloves and stainless steel discs, and boiled ham, lettuce, and a sandwich bun were the ingredients of the deli sandwich. Both NoV GII.4 and the murine NoV 1 (MNV-1, a cultivable human NoV surrogate) were included in the presented study. Transfer of NoV GII.4 and MNV-1 between surfaces was performed by pressing an inoculated donor surface against an acceptor surface. To evaluate the effect of subsequent contact, donor surfaces were pressed a second time to an identical acceptor surface. Subsequently, NoV GII.4 and MNV-1 were detected using real-time reverse transcription PCR assays and plaque assays, respectively. Transfer of both viruses from gloves to stainless steel was inefficient, and virus transfer from food products to stainless steel occurred with inure variability for NoV GII.4 than for MNV-1. Virus transfer from the stainless steel discs to the gloves was substantially more efficient than from the gloves to the stainless steel. NoV GII.4 and MNV-1 transfer from food products to the doves occurred with varying efficiencies, although this variation was more evident for NoV GII.4. The MNV-1 inoculum was significantly less efficiently transferred to the acceptor surface at the second contact, which was not the case for NoV GII.4. The obtained transfer efficiency data may provide insights into the transfer of NoV during preparation of foods and can be included in risk assessment models describing the transmission of NoVs in this context

Protocol for a Scoping/Systematic Review: Scoping Review of Vaccination for the Prevention of Calf Scours in Cow-Calf Operations

Background: The use of antimicrobials in the livestock industry has been a topic of increasing concern in the last  few years. Calf scours is one of the main causes of mortality among calves younger than 1 month and affects the development of the animal, representing severe economic losses to the producers. The causes of the disease include a variety of viral, bacterial and protozoal pathogens, and other non-infectious causes. The treatment efficacy, in particular of antimicrobial therapy, depends on the type of infection. Blanket antimicrobial treatment for calf scours without identification of the pathogen may contribute to antimicrobial resistance. In this review we explore the available literature for evidence of effective methods to prevent calf scours in cow-calf operations in California through the use of vaccination.Objectives:  The objective of this scoping review is to examine and describe the existing literature on vaccination for the prevention of calf scours that might reduce the incidence of calf scours by different causes, and therefore reduce the use of antimicrobials due to calf scours.Design: Primary research on vaccination for pathogens that cause calf scours will be considered for inclusion, such as studies conducted in pre-weaned calves that report the efficacy of vaccines for the prevention of calf scours. The process for selection and inclusion of the studies will be reported in a flow chart according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The results will be summarized in tables and charts describing study types, interventions and outcomes

Acceptability of temporary suspension of visiting during norovirus outbreaks:investigating patient, visitor and public opinion

Background Noroviruses are a leading cause of outbreaks globally and the most common cause of service disruption due to ward closures. Temporary suspension of visiting (TSV) is increasingly a recommended public health measure to reduce exposure, transmission and impact during norovirus outbreaks; however, preventing patient–visitor contact may contravene the ethos of person-centred care, and public acceptability of this measure is not known. Aim To investigate the acceptability of TSV during norovirus outbreaks from the perspectives of patients, visitors and the wider public. Methods Cross-sectional survey of patients (N = 153), visitors (N = 175) and the public (N = 224) in three diverse areas in Scotland. Health Belief Model constructs were applied to understand ratings of acceptability of TSV during norovirus outbreaks, and to determine associations between these levels and various predictor variables. Findings The majority (84.6%) of respondents indicated that the possible benefits of TSV are greater than the possible disadvantages. Conversely, the majority (70%) of respondents disagreed that TSV ‘is wrong as it ignores people's rights to have contact with family and friends’. The majority (81.6%) of respondents agreed that TSV would be more acceptable if exceptions were made for seriously ill or dying patients. Correlational analysis demonstrated that overall acceptability was positively related to perceived severity (r = 0.65), identified benefits (r = 0.54) and implementing additional communication strategies (r = 0.60); acceptability was negatively related to potential barriers (r = −0.49). Conclusions There is greater service user and public support for the use of TSV than concerns around impinging upon patients' rights to have visitors. TSV should be considered as an acceptable infection control measure that could be implemented consistently during norovirus outbreaks