DOCSLIB.ORG

The Norovirus NS3 Protein Is a Dynamic Lipid- and Microtubule-Associated Protein Involved in Viral RNA Replication

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Norovirus NS3 Protein Is a Dynamic Lipid- and Microtubule-Associated Protein Involved in Viral RNA Replication VIRUS-CELL INTERACTIONS crossm The Norovirus NS3 Protein Is a Dynamic Lipid- and Microtubule-Associated Protein Involved in Viral RNA Replication Ben T. Cotton,a,b Jennifer L. Hyde,a,c* Soroush T. Sarvestani,b Stanislav V. Sosnovtsev,d Kim Y. Green,d Peter A. White,e Jason M. Mackenzieb Downloaded from Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria, Australiaa; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australiab; School of Chemical and Biological Sciences, University of Queensland, Brisbane, Queensland, Australiac; Norovirus Gastroenteritis Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USAd; School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, New South Wales, Australiae http://jvi.asm.org/ ABSTRACT Norovirus (NoV) infections are a significant health burden to society, yet the lack of reliable tissue culture systems has hampered the development of appro- Received 31 October 2016 Accepted 18 priate antiviral therapies. Here we show that the NoV NS3 protein, derived from mu- November 2016 Accepted manuscript posted online 23 rine NoV (MNV), is intimately associated with the MNV replication complex and the November 2016 viral replication intermediate double-stranded RNA (dsRNA). We observed that when Citation Cotton BT, Hyde JL, Sarvestani ST, expressed individually, MNV NS3 and NS3 encoded by human Norwalk virus (NV) in- Sosnovtsev SV, Green KY, White PA, Mackenzie duced the formation of distinct vesicle-like structures that did not colocalize with JM. 2017. The norovirus NS3 protein is a dynamic lipid- and microtubule-associated on March 19, 2017 by UQ Library any particular protein markers to cellular organelles but localized to cellular mem- protein involved in viral RNA replication. J Virol branes, in particular those with a high cholesterol content. Both proteins also 91:e02138-16. https://doi.org/10.1128/ showed some degree of colocalization with the cytoskeleton marker ␤-tubulin. Al- JVI.02138-16. though the distribution of MNV and NV NS3s were similar, NV NS3 displayed a Editor Terence S. Dermody, University of Pittsburgh School of Medicine higher level of colocalization with the Golgi apparatus and the endoplasmic reticu- Copyright © 2017 American Society for lum (ER). However, we observed that although both proteins colocalized in mem- Microbiology. All Rights Reserved. branes counterstained with filipin, an indicator of cholesterol content, MNV NS3 dis- Address correspondence to Jason M. played a greater association with flotillin and stomatin, proteins known to associate Mackenzie, [email protected]. with sphingolipid- and cholesterol-rich microdomains. Utilizing time-lapse epifluores- * Present address: Jennifer L. Hyde, Department of Pathology and Immunology, cence microscopy, we observed that the membrane-derived vesicular structures in- Washington University School of Medicine, St. duced by MNV NS3 were highly motile and dynamic in nature, and their movement Louis, Missouri, USA. was dependent on intact microtubules. These results begin to interrogate the func- tions of NoV proteins during virus replication and highlight the conserved properties of the NoV NS3 proteins among the seven Norovirus genogroups. IMPORTANCE Many mechanisms involved in the replication of norovirus still remain unclear, including the role for the NS3 protein, one of seven nonstructural viral pro- teins, which remains to be elucidated. This study reveals that murine norovirus (MNV) NS3 is intimately associated with the viral replication complex and dsRNA. We observed that the NS3 proteins of both MNV and Norwalk virus (NV) induce promi- nent vesicular structures and that this formation is dependent on microtubules and cellular cholesterol. Thus, this study contributes to our understanding of protein function within different Norovirus genogroups and expands a growing knowledge base on the interaction between positive-strand RNA [(ϩ)RNA] viruses and cellu- lar membranes that contribute to the biogenesis of virus-induced membrane or- ganelles. This study contributes to our understanding of viral protein function and the ability of a viral protein to recruit specific cellular organelles and lipids that enable replication. KEYWORDS norovirus, cytoskeleton, virus replication, cellular lipids February 2017 Volume 91 Issue 3 e02138-16 Journal of Virology jvi.asm.org 1 Cotton et al. Journal of Virology oroviruses (NoVs) belong to the Caliciviridae family and are small, nonenveloped, Npositive-sense RNA viruses known to cause acute and chronic diseases in humans (1, 2) and other mammals (3). The clinical symptoms of humans infected with NoV include vomiting, abdominal cramps, and nonbloody loose or watery diarrhea that can lead to severe dehydration (4, 5). NoV infections result in an estimated 230,000 deaths per year, particularly in developing nations (6). This pathogen is highly infectious (7) and transmitted primarily from person to person within enclosed settings such as schools, cruise ships, hospitals, and aged-care and child care facilities (8, 9). NoV is the only virus associated with global pandemics of acute gastroenteritis that emerge every 2 to 3 years, affecting hundreds of millions of people (10, 11). NoV pandemics have occurred globally since the mid-1990s with increasing frequency (10–12). Conse- quently, NoV-associated gastroenteritis has become a major public health concern for which there is no available antiviral agent or preventative vaccine. Downloaded from NoV host cell tropism appears to be exceptionally restricted (13); therefore, human NoVs are difficult to study due to the lack of a reliable cell culture system or any small-animal models. Recently, it was observed that B cells could be infected with human NoV but only in the presence of histo-blood group antigen-expressing enteric bacteria, and infection was observed to be inefficient (14). Subsequently, multiple human NoV strains have been more robustly cultivated in stem cell-derived enterocytes forming human intestinal enteroid monolayer cultures (15). Consequently, the molec- http://jvi.asm.org/ ular mechanisms of human NoV pathogenesis and immunity remain poorly defined (5). In 2003, murine norovirus (MNV) was discovered and has been used to study the immunity and pathogenesis of NoV infection in a mouse model (16). Subsequently, the tropism of MNV for mononuclear cells was identified and led to the establishment of the first in vivo culture system to study NoV replication, a significant advancement in NoV biology (17). NoV harbors an RNA genome of ϳ7,500 nucleotides that is protein linked at the 5= on March 19, 2017 by UQ Library end by VPg (encoded by the viral gene NS5), polyadenylated at the 3= end, and divided into 3 open reading frames (ORFs) (4 for MNV). ORF1 encodes a large polyprotein that undergoes proteolytic cleavage by the virus-encoded protease (NS6) to produce the mature viral nonstructural proteins (18). The two structural proteins, VP1 (major capsid protein) and VP2 (minor capsid protein), are encoded by ORF2 and ORF3, respectively, and can be additionally translated from a viral subgenomic RNA (18). Importantly, the ORF1/ORF2 overlap has been shown to be the breakpoint for genetic recombination (19–22). Our group has been instrumental in identifying and interrogating the intracellular site of MNV replication (20, 21). We have shown that the MNV replication complex (RC) is a collection of irregular-sized vesicles tightly associated with the endoplasmic reticulum (ER), the trans-Golgi network, endosomes, and the centrosome (20, 22). In addition, we have identified the discrete intracellular localization patterns of the MNV ORF1 proteins and their relationship with cellular organelles and membranes utilized during MNV replication (23). We showed that MNV NS1-2 localizes to the ER, NS4 localizes to endosomes, and NS6 localizes to mitochondria (23). Interestingly, NS3 induced discrete vesicular structures that were unidentifiable by typical cell organelle markers but showed some association with microtubules (23, 24). In this study, we aimed to further investigate the function of MNV NS3 during the replication cycle and the origin of the vesicular structures induced by MNV NS3 expression, comparing it to the expression pattern of human NoV (Norwalk virus [NV]) NS3. We show that MNV NS3 is intimately associated with double-stranded RNA (dsRNA) within the MNV RC and show that the localization pattern of transiently expressed human NV NS3 is similar to that of MNV NS3, although there are some subtle differences. Additionally, we show that the vesicular structures induced during NS3 expression contain lipids, and using time-lapse epifluorescence microscopy, we dem- onstrate that these structures are highly dynamic and undergo microtubule-dependent transport. February 2017 Volume 91 Issue 3 e02138-16 jvi.asm.org 2 Norovirus NS3 Protein—Lipids and Microtubules Journal of Virology Downloaded from http://jvi.asm.org/ on March 19, 2017 by UQ Library FIG 1 The MNV NS3 protein associates with the viral replication complex. Thawed cryosections of MNV-infected RAW264.7 cells were fixed at 12 h p.i. (A and B), 18 h p.i. (C and D), or 24 h p.i. (E and F) and were immunolabeled with anti-NS3 antibodies and 10-nm protein A gold. Bars, 200 nm in all cases. RESULTS
Load more

Recommended publications
  • Antibody-Mediated Enhancement of Rabies Virus
    542 Nature Vol. 290 16 April 1981 rearranged, K-chain gene, for example; region than the salivary gland mRNA. It is Are these findings at all relevant to the only one of these is destined to appear in possible that this affects the translation rabies 'early death' effect? Rabies viruses the mRNA, the remainder being removed efficiences of the mRNA (see 'Discussion' were thought to be serologically identical, by differential splicing. in Young et al.). Although the explanation but a number of rabies-related viruses are Why does the mouse go to all this for this fascinating genetic mechanism is now knownl2 , and antigenic variation trouble? Any explanation should consider the subject of future work, it is, of course, between rabies virus strains has been estab­ the fact that a-amylase mRNA accounts likely to be tied up with the primary lished I3 • Mice inoculated with Lagos Bat or for 2 per cent of the cytoplasmic mRNA in question - what determines the different Mokola viruses, two of the rabies-related the salivary gland, but only 0.02 per cent in level of a-amylase in two different tissues? viruses, and subsequently challenged with liver. This level may reflect the transcrip­ In the rat (and other mammals) the rabies virus, also died more quicklyl4. tion rate from the two genes; the 'salivary situation may be even more complicated. These findings suggest that it is not gland' promoter would then be consider­ MacDonald and his co-workers (Nature essential to have homologous neutralizing ably stronger than the 'liver' promoter. 287, 17; 1980) have analysed the rat antibodies to produce the rabies 'early Alternatively, the rate of RNA processing a-amylase genes and these studies point to death' effect, but that cross-reacting sera andlor export to the cytoplasm may be at least five non-allelic a-amylase genes or may also be active in this system as in the different for the two mRNAs.
    [Show full text]
  • Characterizing and Evaluating the Zoonotic Potential of Novel Viruses Discovered in Vampire Bats
    viruses Article Characterizing and Evaluating the Zoonotic Potential of Novel Viruses Discovered in Vampire Bats Laura M. Bergner 1,2,* , Nardus Mollentze 1,2 , Richard J. Orton 2 , Carlos Tello 3,4, Alice Broos 2, Roman Biek 1 and Daniel G. Streicker 1,2 1 Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK; [email protected] (N.M.); [email protected] (R.B.); [email protected] (D.G.S.) 2 MRC–University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK; [email protected] (R.J.O.); [email protected] (A.B.) 3 Association for the Conservation and Development of Natural Resources, Lima 15037, Peru; [email protected] 4 Yunkawasi, Lima 15049, Peru * Correspondence: [email protected] Abstract: The contemporary surge in metagenomic sequencing has transformed knowledge of viral diversity in wildlife. However, evaluating which newly discovered viruses pose sufficient risk of infecting humans to merit detailed laboratory characterization and surveillance remains largely speculative. Machine learning algorithms have been developed to address this imbalance by ranking the relative likelihood of human infection based on viral genome sequences, but are not yet routinely Citation: Bergner, L.M.; Mollentze, applied to viruses at the time of their discovery. Here, we characterized viral genomes detected N.; Orton, R.J.; Tello, C.; Broos, A.; through metagenomic sequencing of feces and saliva from common vampire bats (Desmodus rotundus) Biek, R.; Streicker, D.G. and used these data as a case study in evaluating zoonotic potential using molecular sequencing Characterizing and Evaluating the data.
    [Show full text]
  • Rabies Information for Dog Owners
    Rabies Information for Dog Owners Key Facts Disease in dogs: • During initial days of illness, signs can be nonspecific, such as fever, anxiety and consumption of foreign items (e.g. blankets) • Progresses to more severe signs, such as: • Behavioral change (e.g. aggression, excitability) • Incoordination, loss of balance, disorientation, weakness • Hypersalivation • Seizures • Death results within 10 days of first signs of illness Rabies in dogs is not treatable. Vaccination is key to prevention: • Rabies vaccines are protective if given before exposure to the rabies virus. • Proof of dog vaccination is mandated by many jurisdictions and required for international travel. • Dogs not current on vaccination that are likely exposed to the rabies virus may be required to be euthanized or undergo a long and expensive quarantine. What is it? Rabies is caused by infection with the rabies virus. In North America, the most common wildlife rabies The virus lives in various species of mammals and species (termed reservoirs) vary regionally and is most commonly spread through bites from one include raccoons, skunks, foxes, coyotes, and animal to another or to a human (i.e. in an infected bats. Each year in the United States over 4,000 animal’s saliva). rabid animals are reported, including several Disease in dogs may begin with vague signs of hundred rabid dogs and cats, other domestic illness, but rapidly progresses to severe neurologic species (e.g., horses, cattle, sheep, goats) and signs (e.g. aggression, incoordination). Typically, thousands of wildlife animals. death occurs within 10 days of the first signs of illness. Where is it? The rabies virus is present in nearly all parts of the world.
    [Show full text]
  • Everything You Always Wanted to Know About Rabies Virus ♣♣♣♣♣♣♣♣♣♣♣♣♣♣♣♣♣♣♣♣♣ (But Were Afraid to Ask) Benjamin M
    ANNUAL REVIEWS Further Click here to view this article's online features: t%PXOMPBEmHVSFTBT115TMJEFT t/BWJHBUFMJOLFESFGFSFODFT t%PXOMPBEDJUBUJPOT Everything You Always Wanted t&YQMPSFSFMBUFEBSUJDMFT t4FBSDILFZXPSET to Know About Rabies Virus (But Were Afraid to Ask) Benjamin M. Davis,1 Glenn F. Rall,2 and Matthias J. Schnell1,2,3 1Department of Microbiology and Immunology and 3Jefferson Vaccine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107; email: [email protected] 2Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 Annu. Rev. Virol. 2015. 2:451–71 Keywords First published online as a Review in Advance on rabies virus, lyssaviruses, neurotropic virus, neuroinvasive virus, viral June 24, 2015 transport The Annual Review of Virology is online at virology.annualreviews.org Abstract This article’s doi: The cultural impact of rabies, the fatal neurological disease caused by in- 10.1146/annurev-virology-100114-055157 fection with rabies virus, registers throughout recorded history. Although Copyright c 2015 by Annual Reviews. ⃝ rabies has been the subject of large-scale public health interventions, chiefly All rights reserved through vaccination efforts, the disease continues to take the lives of about 40,000–70,000 people per year, roughly 40% of whom are children. Most of Access provided by Thomas Jefferson University on 11/13/15. For personal use only. Annual Review of Virology 2015.2:451-471. Downloaded from www.annualreviews.org these deaths occur in resource-poor countries, where lack of infrastructure prevents timely reporting and postexposure prophylaxis and the ubiquity of domestic and wild animal hosts makes eradication unlikely. Moreover, al- though the disease is rarer than other human infections such as influenza, the prognosis following a bite from a rabid animal is poor: There is cur- rently no effective treatment that will save the life of a symptomatic rabies patient.
    [Show full text]
  • Eye-Opening Approach to Norovirus Surveillance
    LETTERS Rapid collaboration between pub- DOI: 10.3201/eid1608.091380 of norovirus infections in society. lic health authorities in the Philippines We therefore present a new approach and Finland led to appropriate action References to estimate the number of cases and at the site of origin of the rabies case spread of norovirus infections in the 1. Meslin FX. Rabies as a traveler’s risk, es- within a few days. In a country in pecially in high-endemicity areas. J Travel community. which rabies is not endemic, diagnos- Med. 2005;Suppl 1:S30–40. We plotted the number of queries ing rabies and implementing control 2. Srinivasan A, Burton EC, Kuehnert MJ, for *vomit* (asterisks denote any pre- measures in healthcare settings are of- Rupprecht C, Sutker WL, Ksiazek TG, et fi x or suffi x) submitted to the search al. Rabies in Transplant Recipients Inves- ten diffi cult because of limited experi- tigation Team. Transmission of rabies vi- engine on a medical website in Swe- ence with this disease. The last human rus from an organ donor to four transplant den (www.vardguiden.se). This num- rabies case in Finland was diagnosed recipients. N Engl J Med. 2005;352:1103– ber was normalized to account for in 1985, when a bat researcher died 11. DOI: 10.1056/NEJMoa043018 the increasing use of the website over 3. Metlin AE, Rybakov SS, Gruzdev KN, after being bitten by bats abroad and Neuvonen E, Cox J, Huovilainen A. An- time and aggregated by week, starting in Finland (5). For imported cases, pa- tigenic and molecular characterization of with week 40 in 2005.
    [Show full text]
  • Overview, Prevention, and Treatment of Rabies
    Overview, Prevention, and Treatment of Rabies Andrea Julia Nigg, Pharm.D., and Pamela L. Walker, Pharm.D. Each year, approximately 55,000 individuals worldwide die from an infection due to the rabies virus. Rabies is a life-threatening disease caused by an RNA virus that is usually transmitted to humans through bites from rabid animals. More recently, reports of transmission by means of organ transplantation have been reported. Since human rabies is nearly 100% fatal if prophylactic measures are not followed, an increased awareness of who should receive prophylaxis and when prophylaxis should be administered is necessary. Preexposure prophylaxis entails the administration of the rabies vaccine to individuals at high risk for exposure to rabies viruses (e.g., laboratory workers who handle infected specimens, diagnosticians, veterinarians, animal control workers, rabies researchers, cave explorers). Preexposure prophylaxis involves a three-dose series of the rabies vaccine that may confer some protection from the virus while simplifying postexposure prophylaxis regimens. Postexposure prophylaxis consists of a multimodal approach to decrease an individual’s likelihood of developing clinical rabies after a possible exposure to the virus. Regimens depend on the vaccination status of the victim and involve a combination of wound cleansing, administration of the rabies vaccine, and administration of human rabies immune globulin. If used in a timely and accurate fashion, postexposure prophylaxis is nearly 100% effective. Once clinical manifestations of rabies have developed, however, treatment options for rabies are limited, and to date, only seven individuals have survived rabies virus infection. Treatment of clinical rabies consists of medical support in an intensive care unit, using a multifaceted approach that includes supportive care, heavy sedation, analgesics, anticonvulsants, and antivirals.
    [Show full text]
  • A Scoping Review of Viral Diseases in African Ungulates
    veterinary sciences Review A Scoping Review of Viral Diseases in African Ungulates Hendrik Swanepoel 1,2, Jan Crafford 1 and Melvyn Quan 1,* 1 Vectors and Vector-Borne Diseases Research Programme, Department of Veterinary Tropical Disease, Faculty of Veterinary Science, University of Pretoria, Pretoria 0110, South Africa; [email protected] (H.S.); [email protected] (J.C.) 2 Department of Biomedical Sciences, Institute of Tropical Medicine, 2000 Antwerp, Belgium * Correspondence: [email protected]; Tel.: +27-12-529-8142 Abstract: (1) Background: Viral diseases are important as they can cause significant clinical disease in both wild and domestic animals, as well as in humans. They also make up a large proportion of emerging infectious diseases. (2) Methods: A scoping review of peer-reviewed publications was performed and based on the guidelines set out in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. (3) Results: The final set of publications consisted of 145 publications. Thirty-two viruses were identified in the publications and 50 African ungulates were reported/diagnosed with viral infections. Eighteen countries had viruses diagnosed in wild ungulates reported in the literature. (4) Conclusions: A comprehensive review identified several areas where little information was available and recommendations were made. It is recommended that governments and research institutions offer more funding to investigate and report viral diseases of greater clinical and zoonotic significance. A further recommendation is for appropriate One Health approaches to be adopted for investigating, controlling, managing and preventing diseases. Diseases which may threaten the conservation of certain wildlife species also require focused attention.
    [Show full text]
  • Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus
    viruses Review Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus Renata da Fontoura Budaszewski 1,2 and Veronika von Messling 2,* 1 Laboratório de Virologia, Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre 91540-000, Brazil; [email protected] 2 Veterinary Medicine Division, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen 63225, Germany * Correspondence: [email protected]; Tel.: +49-6103-777-400 Academic Editor: Richard K. Plemper Received: 11 August 2016; Accepted: 30 September 2016; Published: 11 October 2016 Abstract: Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development. Keywords: morbillivirus genus; canine distemper virus; animal models; pathogenesis 1. Introduction Morbilliviruses are enveloped, negative-stranded RNA viruses which cause a moderate to severe respiratory and gastrointestinal disease and long-lasting immunosuppression in their respective hosts. Despite the availability of a safe and cost-effective vaccine, the Measles virus (MeV) remains one of the leading causes of death among young children in developing countries [1].
    [Show full text]
  • IRES Knocks out Rabies
    RESEARCH HIGHLIGHTS VIRAL PATHOGENESIS IRES knocks out rabies Non-segmented negative-strand from poliovirus or human rhinovirus Infection of neurons with RNA RNA viruses that can infect neurons type 2 (HRV2) enables downregula- viruses is initially controlled by in the central nervous system include tion of phosphoprotein expression interferon-β (IFNβ) and subsequently measles virus, mumps virus, Borna at the level of translation and can by virus-specific antibodies and virus, the emerging deadly Nipah render rabies virus avirulent. T-cell derived IFNβ. The rabies virus and Hendra viruses and rabies virus. Although rabies and other phosphoprotein, which is an essential Until now there has been no method non-segmented negative-strand cofactor of the viral polymerase and available to control the expression RNA viruses can replicate in all also has a role in encapsidation of of individual genes of these viruses. cell types, positive-strand RNA replicated genomes, functions to According to a report published in viruses, such as poliovirus and dampen the host response by coun- the Journal of Virology, replacing the HRV2, have a restricted host range. teracting the production of IFN. The transcription signals of the rabies There is evidence that IRESs in the most striking finding from this study virus phosphoprotein gene with 5′-untranslated regions of positive- is that translational attenuation of internal ribosome entry sites (IRESs) strand RNA viruses are subject to phosphoprotein through insertion of cell-type inhibition and can mediate IRESs from poliovirus or HRV2 lim- cell-type specificity. To test whether ited the ability of recombinant rabies Corbis IRESs can affect gene expression of viruses to counteract the production non-segmented negative-strand RNA of IFN, as shown by the failure of viruses, Marschalek et al.
    [Show full text]
  • Genetic and Phenotypic Characterization of a Rabies Virus Strain Isolated from a Dog in Tokyo, Japan in the 1940S
    viruses Article Genetic and Phenotypic Characterization of a Rabies Virus Strain Isolated from a Dog in Tokyo, Japan in the 1940s Tatsuki Takahashi 1, Maho Inukai 2, Michihito Sasaki 3 , Madlin Potratz 4, Supasiri Jarusombuti 5 , Yuji Fujii 6, Shoko Nishiyama 2, Stefan Finke 4 , Kentaro Yamada 7, Hiroki Sakai 1,6,8,9, Hirofumi Sawa 3, Akira Nishizono 7, Makoto Sugiyama 1,2,6 and Naoto Ito 1,2,6,9,* 1 The United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan; [email protected] (T.T.); [email protected] (H.S.); [email protected] (M.S.) 2 Laboratory of Zoonotic Disease, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan; [email protected] (M.I.); [email protected] (S.N.) 3 Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan; [email protected] (M.S.); [email protected] (H.S.) 4 Institute of Molecular Virology and Cell Biology, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany; madlin.potratz@fli.de (M.P.); stefan.finke@fli.de (S.F.) 5 Graduate School of Bioagricultural Science, Nagoya University, Nagoya 464-8601, Japan; [email protected] 6 Joint Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan; [email protected] 7 Department of Microbiology, Faculty of Medicine, Oita University, Oita 879-5593, Japan; [email protected] (K.Y.); [email protected] (A.N.) 8 Laboratory of Veterinary
    [Show full text]
  • 2019 Oral Vaccination to Control Specific Rabies
    RECORD OF DECISION AND FINDING OF NO SIGNIFICANT IMPACT FOR THE ENVIRONEMTNAL ASSESSMENT: ORAL VACCINATION TO CONTROL SPECIFIC RABIES VIRUS VARIANTS WITH HUMAN ADENOVIRUS TYPE 5 VECTOR IN MAINE, NEW HAMPSHIRE, NEW YORK, OHIO, TENNESSEE, VERMONT, VIRGINIA, AND WEST VIRGINIA INTRODUCTION This Record of Decision has been developed by the U.S. Department of Agriculture (USDA), Animal and Plant Health Inspection Service, Wildlife Services (APHIS-WS) in compliance with the requirements of the National Environmental Policy Act (NEPA) of 1969, as amended, the Council on Environmental Quality’s (CEQ) regulations implementing NEPA, as amended, and the USDA and APHIS NEPA implementing regulations and procedures. This Record of Decision documents USDA APHIS’ decision for its Final 2019 Environmental Assessment on Oral Vaccination to Control Specific Rabies Virus Variants with Human Adenovirus Type 5 Vector in Maine, New Hampshire, New York, Ohio, Tennessee, Vermont, Virginia, and West Virginia. APHIS-WS’ decision is to select Alternative 2, the proposed action, to expand the use of ONRAB in the aforementioned states. This Record of Decision (a) states APHIS-WS’ decision, (b) identifies the alternatives and issues considered in reaching the decision and specifies the environmentally preferable alternative, (c) identifies and discusses the factors APHIS-WS balanced in making its decision; and (d) states whether all practical means to minimize environmental harm from implementation of the selected alternative have been adopted. In 2012 the USDA, APHIS-WS program completed an environmental assessment (EA) and that analyzed the potential environmental effects of a proposal to conduct an experimental oral rabies vaccine (ORV) field trial in New Hampshire, New York, Ohio, Vermont, and West Virginia using the human adenovirus type 5 rabies glycoprotein recombinant (AdRG1.3; trade name ONRAB, Artemis Technologies, Inc., Guelph, ON) vaccine.
    [Show full text]
  • Downloads/ Hsp90interactors.Pdf), and Tend to Be Metastable, Being Rapidly Degraded Upon Hsp90 Inhibition
    viruses Review Chaperoning the Mononegavirales: Current Knowledge and Future Directions Victor Latorre †, Florian Mattenberger † and Ron Geller * Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSIC, 46980 Valencia, Spain; [email protected] (V.L.); [email protected] (F.M.) * Correspondence: [email protected]; Tel.: +34-963-543-187 † These authors contributed equally to this work. Received: 16 November 2018; Accepted: 5 December 2018; Published: 8 December 2018 Abstract: The order Mononegavirales harbors numerous viruses of significant relevance to human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses, and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread. Therefore, targeting cellular pathways used by viruses can provide novel therapeutic approaches. One of the key challenges confronted by both hosts and viruses alike is the successful folding and maturation of proteins. In cells, this task is faced by cellular molecular chaperones, a group of conserved and abundant proteins that oversee protein folding and help maintain protein homeostasis. In this review, we summarize the current knowledge of how the Mononegavirales interact with cellular chaperones, highlight key gaps in our knowledge, and discuss the potential of chaperone inhibitors as antivirals. Keywords: Mononegavirales; chaperones; antivirals; Hsp70;
    [Show full text]