RESUMEN
Human norovirus (HuNoV) is the leading causative agent of foodborne disease outbreaks worldwide. HuNoV is highly stable, contagious, and only a few virus particles can cause illness. However, HuNoV is difficult to study because of the lack of an efficient in vitro cell culture system or a small animal model. To date, there is very limited information available about the biology of HuNoV, with most data coming from the study of surrogates, such as HuNoV virus-like particle (VLP), murine norovirus (MNV), and feline calicivirus (FCV). High-risk foods for HuNoV contamination include seafood, fresh produce, and ready-to-eat foods. Currently, there is no effective measure to control HuNoV outbreaks; thus, development of food-processing technologies to inactivate HuNoV in these high-risk foods is urgently needed. Although a VLP-based vaccine induces humoral, mucosal, and cellular immunities in animals and currently is in human clinical trials, development of other new vaccine candidates, such as live vectored vaccines, should be considered. Recent evidence suggests that blockage of virus-receptor interaction may be a promising antiviral target. To enhance our capability to combat this important agent, there is an urgent need to develop multidisciplinary, multi-institutional integrated research and to implement food virology education and extension programs nationwide.
Asunto(s)
Infecciones por Caliciviridae/prevención & control , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/prevención & control , Gastroenteritis/prevención & control , Norovirus/crecimiento & desarrollo , Animales , Antivirales/uso terapéutico , Infecciones por Caliciviridae/inmunología , Infecciones por Caliciviridae/virología , Modelos Animales de Enfermedad , Manipulación de Alimentos/métodos , Enfermedades Transmitidas por los Alimentos/inmunología , Enfermedades Transmitidas por los Alimentos/virología , Gastroenteritis/inmunología , Gastroenteritis/virología , Humanos , Viabilidad Microbiana , Norovirus/inmunología , Vacunas Virales/uso terapéuticoRESUMEN
Gamma irradiation is a nonthermal processing technology that has been used for the preservation of a variety of food products. This technology has been shown to effectively inactivate bacterial pathogens. Currently, the FDA has approved doses of up to 4.0 kGy to control food-borne pathogens in fresh iceberg lettuce and spinach. However, whether this dose range effectively inactivates food-borne viruses is less understood. We have performed a systematic study on the inactivation of a human norovirus surrogate (murine norovirus 1 [MNV-1]), human norovirus virus-like particles (VLPs), and vesicular stomatitis virus (VSV) by gamma irradiation. We demonstrated that MNV-1 and human norovirus VLPs were resistant to gamma irradiation. For MNV-1, only a 1.7- to 2.4-log virus reduction in fresh produce at the dose of 5.6 kGy was observed. However, VSV was more susceptible to gamma irradiation, and a 3.3-log virus reduction at a dose of 5.6 kGy in Dulbecco's modified Eagle medium (DMEM) was achieved. We further demonstrated that gamma irradiation disrupted virion structure and degraded viral proteins and genomic RNA, which resulted in virus inactivation. Using human norovirus VLPs as a model, we provide the first evidence that the capsid of human norovirus has stability similar to that of MNV-1 after exposure to gamma irradiation. Overall, our results suggest that viruses are much more resistant to irradiation than bacterial pathogens. Although gamma irradiation used to eliminate the virus contaminants in fresh produce by the FDA-approved irradiation dose limits seems impractical, this technology may be practical to inactivate viruses for other purposes, such as sterilization of medical equipment.
Asunto(s)
Desinfección/métodos , Rayos gamma , Viabilidad Microbiana/efectos de la radiación , Norovirus/efectos de la radiación , Vesiculovirus/efectos de la radiación , Virosomas/efectos de la radiación , Inactivación de Virus , Microbiología de Alimentos/métodos , Enfermedades Transmitidas por los Alimentos/prevención & control , Fragaria/virología , Humanos , Lactuca/virología , Spinacia oleracea/virologíaRESUMEN
BACKGROUND: Recently, using a mouse model of mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease with severe neurological deterioration, we showed that MPS IIIB neuropathology is accompanied by a robust neuroinflammatory response of unknown consequence. This study was to assess whether MPS IIIB lymphocytes are pathogenic. METHODS: Lymphocytes from MPS IIIB mice were adoptively transferred to naïve wild-type mice. The recipient animals were then evaluated for signs of disease and inflammation in the central nervous system. RESULTS: Our results show for the first time, that lymphocytes isolated from MPS IIIB mice caused a mild paralytic disease when they were injected systemically into naïve wild-type mice. This disease is characterized by mild tail and lower trunk weakness with delayed weight gain. The MPS IIIB lymphocytes also trigger neuroinflammation within the CNS of recipient mice characterized by an increase in transcripts of IL2, IL4, IL5, IL17, TNFalpha, IFNalpha and Ifi30, and intraparenchymal lymphocyte infiltration. CONCLUSIONS: Our data suggest that an autoimmune response directed at CNS components contributes to MPS IIIB neuropathology independent of lysosomal storage pathology. Adoptive transfer of purified T-cells will be needed in future studies to identify specific effector T-cells in MPS IIIB neuroimmune pathogenesis.
Asunto(s)
Autoinmunidad , Sistema Nervioso Central/inmunología , Mucopolisacaridosis III , Traslado Adoptivo , Animales , Trasplante de Células , Sistema Nervioso Central/anatomía & histología , Sistema Nervioso Central/fisiología , Citocinas/genética , Citocinas/inmunología , Humanos , Linfocitos/citología , Linfocitos/inmunología , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Mucopolisacaridosis III/inmunología , Mucopolisacaridosis III/patología , Mucopolisacaridosis III/fisiopatología , Prueba de Desempeño de Rotación con Aceleración Constante , Bazo/citologíaRESUMEN
Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with severe neurological manifestations due to alpha-N-acetylglucosaminidase (NaGlu) deficiency. The mechanism of neuropathology in MPS IIIB is unclear. This study investigates the role of immune responses in neurological disease of MPS IIIB in mice. By means of gene expression microarrays and real-time quantitative reverse transcriptase-polymerase chain reaction, we demonstrated significant up-regulation of numerous immune-related genes in MPS IIIB mouse brain involving a broad range of immune cells and molecules, including T cells, B cells, microglia/macrophages, complement, major histocompatibility complex class I, immunoglobulin, Toll-like receptors, and molecules essential for antigen presentation. The significantly enlarged spleen and lymph nodes in MPS IIIB mice were due to an increase in splenocytes/lymphocytes, and functional assays indicated that the T cells were activated. An autoimmune component to the disease was further suggested by the presence of putative autoantigen or autoantigens in brain extracts that reacted specifically with serum IgG from MPS IIIB mice. We also demonstrated for the first time that immunosuppression with prednisolone alone can significantly slow the central nervous system disease progression. Our data indicate that immune responses contribute greatly to the neuropathology of MPS IIIB and should be considered as an adjunct treatment in future therapeutic developments for optimal therapeutic effect.