Murine Noroviruses Comprising a Single Genogroup Exhibit Biological Diversity despite Limited Sequence Divergence

Thackray, Larissa B.; Wobus, Christiane E.; Chachu, Karen A.; Liu, Bo; Alegre, Eric R.; Henderson, Keith; Kelley, Scott T.; Virgin, Herbert W.

doi:10.1128/jvi.00783-07

Cited by 243 publications

(412 citation statements)

References 81 publications

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“…However, due to the lack of an efficient cell culture or animal model, direct evaluation of human NoV serotypes remains challenging. The most widely used MNV surrogate model exhibits little genetic and antigenic variation and all laboratory strains belong to the same serotype (Thackray et al, 2007).…”

Section: Antigenic Diversity and Serotypesmentioning

confidence: 99%

Rhesus enteric calicivirus surrogate model for human norovirus gastroenteritis

Farkas

2015

Journal of General Virology

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Human noroviruses are one of the major causes of acute gastroenteritis worldwide. Due to the lack of an efficient human norovirus cell culture system coupled with an animal model, human norovirus research mainly relies on human volunteer studies and surrogate models. Current models either utilize human norovirus-infected animals including the gnotobiotic pig or calf and the chimpanzee models, or employ other members of the family Caliciviridae including cell culture propagable surrogate caliciviruses such as the feline calicivirus, murine norovirus and most recently the Tulane virus. One of the major features of human noroviruses is their extreme biological diversity, including genetic, antigenic and histo-blood group antigen binding diversity, and possible differences of virulence and environmental stability. This extreme biological diversity and its effect on intervention/prevention strategies cannot be modelled by uniform groups of surrogates, much less by single isolates. Tulane virus, the prototype recovirus strain, was discovered in 2008. Since then, several other novel recoviruses have been described and cell culture adapted. Recent studies indicate that the epidemiology, the biological features and diversity of recoviruses and the course of infection and clinical disease in recovirus-infected macaques more closely reflect those properties of human noroviruses than any of the current surrogates. This review aims to summarize what is currently known about recoviruses, highlight their biological similarities to human noroviruses and discuss applications of the model in addressing questions relevant for human norovirus research.

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Section: Antigenic Diversity and Serotypesmentioning

confidence: 99%

Rhesus enteric calicivirus surrogate model for human norovirus gastroenteritis

Farkas

2015

Journal of General Virology

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“…ORF-1 encodes the non-structural proteins, whereas ORF-2 and ORF-3 encode structural proteins (Sosnovtsev et al, 2006). ORF-4 was recently identified within the MNV-1 genome and encodes a single protein of unknown function (Thackray et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Murine norovirus-1 cell entry is mediated through a non-clathrin-, non-caveolae-, dynamin- and cholesterol-dependent pathway

Gerondopoulos

Jackson

Monaghan

et al. 2010

Journal of General Virology

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For many viruses, endocytosis and exposure to the low pH within acidic endosomes is essential for infection. It has previously been reported that feline calicivirus uses clathrin-mediated endocytosis for entry into mammalian cells. Here, we report that infection of RAW264.7 macrophages by the closely related murine norovirus-1 (MNV-1) does not require the clathrin pathway, as infection was not inhibited by expression of dominant-negative Eps15 or by knockdown of the adaptin-2 complex. Further, infection was not inhibited by reagents that raise endosomal pH. RAW264.7 macrophages were shown not to express caveolin, and flotillin depletion did not inhibit infection, suggesting that caveolae and the flotillin pathway are not required for cell entry. However, MNV-1 infection was inhibited by methyl-b-cyclodextrin and the dynamin inhibitor, dynasore. Addition of these drugs to the cells after a period of virus internalization did not inhibit infection, suggesting the involvement of cholesterol-sensitive lipid rafts and dynamin in the entry mechanism. Macropinocytosis (MPC) was shown to be active in RAW264.7 macrophages (as indicated by uptake of dextran) and could be blocked by 5-(N-ethyl-N-isopropyl) amiloride (EIPA), which is reported to inhibit this pathway. However, infection was enhanced in the presence of EIPA. Similarly, actin disruption, which also inhibits MPC, resulted in enhanced infection. These results suggest that MPC could contribute to virus degradation or that inhibition of MPC could lead to the upregulation of other endocytic pathways of virus uptake. INTRODUCTIONThe family Caliciviridae is divided into four genera: Vesivirus, Lagovirus, Sapovirus and Norovirus. The human noroviruses are the most common cause of acute viral gastroenteritis, especially in industrialized countries (Lopman et al., 2003); there is currently no treatment or vaccine for these viruses. In addition, there is still no routine tissue culture system for the propagation of human noroviruses, but the recent discovery of murine norovirus-1 (MNV-1) has provided an efficient model system for the study of norovirus replication, as this virus replicates efficiently in murine macrophages and dendritic cells (DCs) (Karst et al., 2003;Wobus et al., 2004). MNV-1 is highly prevalent in laboratory mice and has been shown to be lethal to mice with impaired innate immunity (Hsu et al., 2006;Karst et al., 2003;Muller et al., 2007).Noroviruses are non-enveloped and contain a singlestranded RNA genome of about 7.3 kb, which is linked to the viral VPg protein at the 59 end and is polyadenylated at the 39 end (Karst et al., 2003;Wobus et al., 2004). The genome is organized into four open reading frames (ORF-1-4). ORF-1 encodes the non-structural proteins, whereas ORF-2 and ORF-3 encode structural proteins (Sosnovtsev et al., 2006). ORF-4 was recently identified within the MNV-1 genome and encodes a single protein of unknown function (Thackray et al., 2007).For many viruses, infection requires virus uptake by endocytosis. A number of different endo...

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“…Generally, MNV infection does not show any clinical symptoms in immunocompetent mice [23], except for occasional association with histopathological changes in the intestine and the spleen [14]. On the other hand, it sometimes induces noticeable symptoms such as diarrhea in immunodeficient mice, such as OTI/Rag1 -/-IFN-g -/-and b 2 M -/-mice [20]. Persistent MNV infection has been reported in not only immunodeficient but also immunocompetent mice [4,6,14].…”

Section: Introductionmentioning

confidence: 99%

“…Genetic analysis of this agent has revealed that the pathogen (MNV-1) is close--Original-ly related to human norovirus, a member of the Caliciviridae family of positive-strand RNA viruses. In addition to MNV-1, several MNV strains have been isolated from laboratory mice [6,10,20]. Generally, MNV infection does not show any clinical symptoms in immunocompetent mice [23], except for occasional association with histopathological changes in the intestine and the spleen [14].…”

Section: Introductionmentioning

confidence: 99%

Indirect ELISA and Indirect Immunofluorescent Antibody Assay for Detecting the Antibody against Murine Norovirus S7 in Mice

et al. 2010

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Abstract:To evaluate murine norovirus (MNV) infection in laboratory mice, we attempted to develop an enzyme-linked immunosorbent assay (ELISA) system and an indirect immunofluorescent antibody (IFA) assay for detecting the anti-MNV-S7 antibody in mice. MNV-S7, which was isolated in Japan, was used in both assays. The antigen for ELISA was prepared by ultracentrifugation of culture supernatants of RAW 264 cells infected with MNV-S7. Positive sera were obtained from 6-week-old, female C57BL/6JJcl mice inoculated orally with MNV-S7. IFA against infected RAW 264 cells was able to discriminate positive sera from negative sera. Indirect ELISA was performed using 96-well ELISA plates coated with formalintreated MNV-S7 antigen. In this ELISA system, mouse sera obtained 2 weeks after infection or later showed significantly high OD values and were judged positive. An equal level of anti-MNV-S7 antibody response was observed in BALB/cAJcl, C57BL/6JJcl, DBA/2JJcl, and Jcl:ICR mice; whereas, C3H/HeJJcl mice demonstrated slightly lower antibody production 4 weeks after infection. We also used this ELISA system to evaluate 77 murine serum samples obtained from 15 conventional mouse rooms in research facilities in Japan and found that approximately half of the serum samples contained antibody to MNV-S7. We found that some serum samples were negative for antibodies to mouse hepatitis virus and Mycoplasma pulmonis but positive for antibody to MNV-S7. The results suggest that the MNV infection is more prevalent than other infections such as mouse hepatitis virus and Mycoplasma pulmonis in conventional mouse colonies in Japan, as is the case in other areas of the world.

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Murine Noroviruses Comprising a Single Genogroup Exhibit Biological Diversity despite Limited Sequence Divergence

Abstract: Viruses within the genus

Cited by 243 publications

References 81 publications

Rhesus enteric calicivirus surrogate model for human norovirus gastroenteritis

Rhesus enteric calicivirus surrogate model for human norovirus gastroenteritis

Murine norovirus-1 cell entry is mediated through a non-clathrin-, non-caveolae-, dynamin- and cholesterol-dependent pathway

Indirect ELISA and Indirect Immunofluorescent Antibody Assay for Detecting the Antibody against Murine Norovirus S7 in Mice

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