scholarly journals A Mouse Model for Studying Viscerotropic Disease Caused by Yellow Fever Virus Infection

2009 ◽  
Vol 5 (10) ◽  
pp. e1000614 ◽  
Author(s):  
Kathryn C. Meier ◽  
Christina L. Gardner ◽  
Mikhail V. Khoretonenko ◽  
William B. Klimstra ◽  
Kate D. Ryman
Keyword(s):  
Virus Infection ◽  
Mouse Model ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus

scholarly journals Castanospermine, a Potent Inhibitor of Dengue Virus Infection In Vitro and In Vivo

2005 ◽  
Vol 79 (14) ◽  
pp. 8698-8706 ◽  
Author(s):  
Kevin Whitby ◽  
Theodore C. Pierson ◽  
Brian Geiss ◽  
Kelly Lane ◽  
Michael Engle ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Virus Infection ◽  
Mouse Model ◽  
Dengue Virus ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
West Nile ◽  
Dengue Virus Infection

ABSTRACT Previous studies have suggested that α-glucosidase inhibitors such as castanospermine and deoxynojirimycin inhibit dengue virus type 1 infection by disrupting the folding of the structural proteins prM and E, a step crucial to viral secretion. We extend these studies by evaluating the inhibitory activity of castanospermine against a panel of clinically important flaviviruses including all four serotypes of dengue virus, yellow fever virus, and West Nile virus. Using in vitro assays we demonstrated that infections by all serotypes of dengue virus were inhibited by castanospermine. In contrast, yellow fever virus and West Nile virus were partially and almost completely resistant to the effects of the drug, respectively. Castanospermine inhibited dengue virus infection at the level of secretion and infectivity of viral particles. Importantly, castanospermine prevented mortality in a mouse model of dengue virus infection, with doses of 10, 50, and 250 mg/kg of body weight per day being highly effective at promoting survival (P ≤ 0.0001). Correspondingly, castanospermine had no adverse or protective effect on West Nile virus mortality in an analogous mouse model. Overall, our data suggest that castanospermine has a strong antiviral effect on dengue virus infection and warrants further development as a possible treatment in humans.

scholarly journals Host-Specific NS5 Ubiquitination Determines Yellow Fever Virus Tropism

2019 ◽  
Vol 93 (14) ◽  
Author(s):  
Lisa Miorin ◽  
Maudry Laurent-Rolle ◽  
Giuseppe Pisanelli ◽  
Pierre Hendrick Co ◽  
Randy A. Albrecht ◽  
...  
Keyword(s):  
Animal Models ◽  
Mouse Model ◽  
Yellow Fever ◽  
Zika Virus ◽  
Yellow Fever Virus ◽  
Disease Model ◽  
Fever Virus ◽  
Type I ◽  
Human Pathogens ◽  
Immunocompetent Mouse

ABSTRACT The recent yellow fever virus (YFV) epidemic in Brazil in 2017 and Zika virus (ZIKV) epidemic in 2015 serve to remind us of the importance of flaviviruses as emerging human pathogens. With the current global flavivirus threat, there is an urgent need for antivirals and vaccines to curb the spread of these viruses. However, the lack of suitable animal models limits the research questions that can be answered. A common trait of all flaviviruses studied thus far is their ability to antagonize interferon (IFN) signaling so as to enhance viral replication and dissemination. Previously, we reported that YFV NS5 requires the presence of type I IFN (IFN-α/β) for its engagement with human signal transducer and activator of transcription 2 (hSTAT2). In this manuscript, we report that like the NS5 proteins of ZIKV and dengue virus (DENV), YFV NS5 protein is able to bind hSTAT2 but not murine STAT2 (mSTAT2). Contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, replacing mSTAT2 with hSTAT2 cannot rescue the YFV NS5-STAT2 interaction, as YFV NS5 is also unable to interact with hSTAT2 in murine cells. We show that the IFN-α/β-dependent ubiquitination of YFV NS5 that is required for STAT2 binding in human cells is absent in murine cells. In addition, we demonstrate that mSTAT2 restricts YFV replication in vivo. These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses. IMPORTANCE Flaviviruses such as yellow fever virus (YFV), Zika virus (ZIKV), and dengue virus (DENV) are important human pathogens. A common flavivirus trait is the antagonism of interferon (IFN) signaling to enhance viral replication and spread. We report that like ZIKV NS5 and DENV NS5, YFV NS5 binds human STAT2 (hSTAT2) but not mouse STAT2 (mSTAT2), a type I IFN (IFN-α/β) pathway component. Additionally, we show that contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, YFV NS5 is unable to interact with hSTAT2 in murine cells. We demonstrate that mSTAT2 restricts YFV replication in mice and that this correlates with a lack of IFN-α/β-induced YFV NS5 ubiquitination in murine cells. The lack of suitable animal models limits flavivirus pathogenesis, vaccine, and drug research. These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses.

scholarly journals Yellow Fever Virus/Dengue-2 Virus and Yellow Fever Virus/Dengue-4 Virus Chimeras: Biological Characterization, Immunogenicity, and Protection against Dengue Encephalitis in the Mouse Model

2003 ◽  
Vol 77 (6) ◽  
pp. 3655-3668 ◽  
Author(s):  
Thomas J. Chambers ◽  
Yan Liang ◽  
Deborah A. Droll ◽  
Jacob J. Schlesinger ◽  
Andrew D. Davidson ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dengue Virus ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
E Proteins ◽  
Dengue Viruses ◽  
Intracerebral Inoculation ◽  
Intraperitoneal Route ◽  
Chimeric Viruses

ABSTRACT Two yellow fever virus (YFV)/dengue virus chimeras which encode the prM and E proteins of either dengue virus serotype 2 (dengue-2 virus) or dengue-4 virus within the genome of the YFV 17D strain (YF5.2iv infectious clone) were constructed and characterized for their properties in cell culture and as experimental vaccines in mice. The prM and E proteins appeared to be properly processed and glycosylated, and in plaque reduction neutralization tests and other assays of antigenic specificity, the E proteins exhibited profiles which resembled those of the homologous dengue virus serotypes. Both chimeric viruses replicated in cell lines of vertebrate and mosquito origin to levels comparable to those of homologous dengue viruses but less efficiently than the YF5.2iv parent. YFV/dengue-4 virus, but not YFV/dengue-2 virus, was neurovirulent for 3-week-old mice by intracerebral inoculation; however, both viruses were attenuated when administered by the intraperitoneal route in mice of that age. Single-dose inoculation of either chimeric virus at a dose of 105 PFU by the intraperitoneal route induced detectable levels of neutralizing antibodies against the homologous dengue virus strains. Mice which had been immunized in this manner were fully protected from challenge with homologous neurovirulent dengue viruses by intracerebral inoculation compared to unimmunized mice. Protection was associated with significant increases in geometric mean titers of neutralizing antibody compared to those for unimmunized mice. These data indicate that YFV/dengue virus chimeras elicit antibodies which represent protective memory responses in the mouse model of dengue encephalitis. The levels of neurovirulence and immunogenicity of the chimeric viruses in mice correlate with the degree of adaptation of the dengue virus strain to mice. This study supports ongoing investigations concerning the use of this technology for development of a live attenuated viral vaccine against dengue viruses.

Congenital Yellow Fever Virus Infection after Immunization in Pregnancy

1993 ◽  
Vol 168 (6) ◽  
pp. 1520-1523 ◽  
Author(s):  
T. F. Tsai ◽  
R. Paul ◽  
M. C. Lynberg ◽  
G. W. Letson
Keyword(s):  
Virus Infection ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
In Pregnancy

scholarly journals Comparison of the inhibitory effects of interferon alfacon-1 and ribavirin on yellow fever virus infection in a hamster model

2007 ◽  
Vol 73 (2) ◽  
pp. 140-146 ◽  
Author(s):  
Justin G. Julander ◽  
John D. Morrey ◽  
Lawrence M. Blatt ◽  
Kristiina Shafer ◽  
Robert W. Sidwell
Keyword(s):  
Virus Infection ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Inhibitory Effects ◽  
Hamster Model

scholarly journals A Yellow Fever Virus 17D Infection and Disease Mouse Model Used to Evaluate a Chimeric Binjari-Yellow Fever Virus Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 368 ◽  
Author(s):  
Kexin Yan ◽  
Laura J. Vet ◽  
Bing Tang ◽  
Jody Hobson-Peters ◽  
Daniel J. Rawle ◽  
...  
Keyword(s):  
Weight Loss ◽  
Mouse Model ◽  
Yellow Fever ◽  
Virus Vaccine ◽  
Neutralizing Antibodies ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Liver Pathology ◽  
Vaccine Production ◽  
Mosquito Cells

Despite the availability of an effective, live attenuated yellow fever virus (YFV) vaccine (YFV 17D), this flavivirus still causes up to ≈60,000 deaths annually. A number of new approaches are seeking to address vaccine supply issues and improve safety for the immunocompromised vaccine recipients. Herein we describe an adult female IFNAR-/- mouse model of YFV 17D infection and disease that recapitulates many features of infection and disease in humans. We used this model to evaluate a new YFV vaccine that is based on a recently described chimeric Binjari virus (BinJV) vaccine technology. BinJV is an insect-specific flavivirus and the chimeric YFV vaccine (BinJ/YFV-prME) was generated by replacing the prME genes of BinJV with the prME genes of YFV 17D. Such BinJV chimeras retain their ability to replicate to high titers in C6/36 mosquito cells (allowing vaccine production), but are unable to replicate in vertebrate cells. Vaccination with adjuvanted BinJ/YFV-prME induced neutralizing antibodies and protected mice against infection, weight loss and liver pathology after YFV 17D challenge.

scholarly journals Experimental Yellow Fever Virus Infection in the Golden Hamster(Mesocricetus auratus).I. Virologic, Biochemical, and Immunologic Studies

2001 ◽  
Vol 183 (10) ◽  
pp. 1431-1436 ◽  
Author(s):  
Robert B. Tesh ◽  
Hilda Guzman ◽  
Amelia P. A. Travassos da Rosa ◽  
Pedro F. C. Vasconcelos ◽  
Leonidas B. Dias ◽  
...  
Keyword(s):  
Virus Infection ◽  
Yellow Fever ◽  
Golden Hamster ◽  
Yellow Fever Virus ◽  
Mesocricetus Auratus ◽  
Fever Virus

Prevalence of Yellow fever virus infection and associated factors among acute febrile patients in Arbaminch districts, Southern Ethiopia

2020 ◽  
Author(s):  
Daniel Eshetu ◽  
Tsegaye Alemayehu ◽  
Temesgen bizuayehu Wube
Keyword(s):  
Virus Infection ◽  
Yellow Fever ◽  
Associated Factors ◽  
Yellow Fever Virus ◽  
Laboratory Finding ◽  
Clinical Signs ◽  
Fever Virus ◽  
Southern Ethiopia ◽  
P Value ◽  
Age Group

Abstract Yellow fever is a rapidly emerging arthropod-borne viral infection, which causes considerable illness and death worldwide. However, little is known regarding the epidemiology of yellow fever virus infection in Ethiopia where mosquito-borne diseases like malaria are common. This study aimed to determine the seroprevalence of yellow fever virus infection and its associated factors among febrile illness in Arbaminch districts in Southern Ethiopia. An institution-based cross-sectional study was conducted in a consecutive group of 529 acute febrile patients between May to August 2016. Data on socio-demographic, environmental and clinical signs and symptoms were collected using structured questionnaires. Serum was used to detect anti-yellow fever virus IgG and/or IgM using indirect Immunofluorescent assay (Euro immune Biochip mosaics, Lübeck, Germany). A logistic regression analysis was done using SPSS V-20 (IBM Corp, 2012). P-value < 0.05 was taken as statistically significant. Of the tested 529 serum samples 14.9% and 7.2% were positive for anti-yellow fever IgG and IgM respectively. Among IgG positive patients, males accounted for 15.04% and female 14.85%. Yellow fever exposure was more in the younger age group; participants age less than 20 years (26.80%), followed by those in the age group above 60 years (26.47%). Further, the prevalence of yellow fever exposure among urban residents was 37.14%. Of the assessed risk factors, only constitutional symptoms were significantly associated with the Yellow fever virus (AOR = 0.28, 95% CI 0.30- 0.72.P < 0.011). The laboratory finding of this study shows, the level of exposure to yellow fever among febrile cases is relatively high; however, clinical diagnosis of febrile patients is a common practice in the study area. Therefore, Domestication and routine performance of yellow fever virus differential diagnosis will help to address the phenomenon of the virus.

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