Animal models of highly pathogenic RNA viral infections: Hemorrhagic fever viruses

2008 ◽  
Vol 78 (1) ◽  
pp. 79-90 ◽  
Author(s):  
Brian B. Gowen ◽  
Michael R. Holbrook
Keyword(s):  
Animal Models ◽  
Viral Infections ◽  
Hemorrhagic Fever ◽  
Highly Pathogenic

scholarly journals Machupo virus with mutations in the transmembrane domain and glycosylation sites is attenuated and immunogenic in animal models of Bolivian Hemorrhagic Fever

2021 ◽  
Author(s):  
Emily K Mantlo ◽  
Junki Maruyama ◽  
John T Manning ◽  
Timothy G Wanninger ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Animal Models ◽  
Mouse Model ◽  
Guinea Pigs ◽  
Rational Design ◽  
Transmembrane Domain ◽  
Vaccine Development ◽  
Hemorrhagic Fever ◽  
Highly Pathogenic ◽  
Glycosylation Sites ◽  
Machupo Virus

AbstractSeveral highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans, for which vaccines and antivirals are limited or unavailable. New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuate MACV in an IFN-αβ/γ receptor knockout mouse model. However, some capability to induce neurological pathology still remained. Highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. A F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in GPC TMD. The MACV mutant is fully attenuated in IFN-αβ/γ receptor knockout mice and outbred guinea pigs. Furthermore, inoculation with this mutant MACV fully protected guinea pigs from wild-type MACV lethal challenge. Lastly, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which informs the rational design of potential vaccine candidates for highly pathogenic arenaviruses.ImportanceFor arenaviruses, the only vaccine available is the live-attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. Nevertheless, mutating either of them is not sufficient for full and stable attenuation of JUNV. Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC, and also introduced the corresponding F438I substitution in the GPC TMD. This MACV mutant is fully attenuated in two animal models and protects animals from lethal infection. Thus, our studies highlight the feasibility of rational attenuation of highly pathogenic arenaviruses for vaccine development. Another important finding from this study is that the F438I substitution in GPC TMD could substantially affect MACV replication in neurons. Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism.

scholarly journals Pathogen Dose in Animal Models of Hemorrhagic Fever Virus Infections and the Potential Impact on Studies of the Immune Response

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 275
Author(s):  
Bryce M. Warner
Keyword(s):  
Immune Response ◽  
Animal Models ◽  
Hemorrhagic Fever ◽  
Virus Infections ◽  
Critical Determinant ◽  
Animal Models Of Disease ◽  
Hemorrhagic Fever Virus ◽  
Immune Correlates ◽  
Clinical Drug Development ◽  
Wide Range

Viral hemorrhagic fever viruses come from a wide range of virus families and are a significant cause of morbidity and mortality worldwide each year. Animal models of infection with a number of these viruses have contributed to our knowledge of their pathogenesis and have been crucial for the development of therapeutics and vaccines that have been approved for human use. Most of these models use artificially high doses of virus, ensuring lethality in pre-clinical drug development studies. However, this can have a significant effect on the immune response generated. Here I discuss how the dose of antigen or pathogen is a critical determinant of immune responses and suggest that the current study of viruses in animal models should take this into account when developing and studying animal models of disease. This can have implications for determination of immune correlates of protection against disease as well as informing relevant vaccination and therapeutic strategies.

scholarly journals An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Zhang ◽  
Shuaiyin Chen ◽  
Weiguo Zhang ◽  
Haiyan Yang ◽  
Yuefei Jin ◽  
...  
Keyword(s):  
Animal Models ◽  
Severe Acute Respiratory Syndrome ◽  
Research Progress ◽  
Laboratory Mice ◽  
Disease Manifestation ◽  
Highly Pathogenic ◽  
The World ◽  
Coronavirus Infection ◽  
Different Levels ◽  
Critical Aspects

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of highly pathogenic coronavirus animal model is beneficial for the study of vaccines and pathogenic mechanism of the virus. Laboratory mice, Syrian hamsters, Non-human primates and Ferrets have been used to establish animal models of emerging coronavirus infection. Different animal models can reproduce clinical infection symptoms at different levels. Appropriate animal models are of great significance for the pathogenesis of COVID-19 and the research progress related to vaccines. This review aims to introduce the current progress about experimental animal models for SARS-CoV-2, and collectively generalize critical aspects of disease manifestation in humans and increase their usefulness in research into COVID-19 pathogenesis and developing new preventions and treatments.

scholarly journals Current status of major foodborne and waterborne viral infections and their prevention strategies

2021 ◽  
Vol 7 (3) ◽  
pp. 227-241
Author(s):  
Ahmet Gökhan Coşkun ◽  
Ayşegül Demircioğlu ◽  
Seran Temelli ◽  
Ayşegül Eyigör
Keyword(s):  
Viral Infections ◽  
Hemorrhagic Fever ◽  
Diagnostic Techniques ◽  
Control Measures ◽  
Current Status ◽  
Waterborne Diseases ◽  
Antiviral Compounds ◽  
Current Prevalence ◽  
Haccp System ◽  
Waterborne Viruses

Advances in diagnostic techniques and their widespread use for infectious agents revealed the considerably high current prevalence of viral agents in foodborne and waterborne diseases. Foodborne and waterborne viruses are indicated to cause not only gastroenteritis and hepatitis but also neurological disorders, respiratory tract diseases, myocarditis, glomerulonephritis and hemorrhagic fever, with a particularly high mortality rate in infants/children and in individuals with immune deficiency. Additionally, due to their resistance to environmental conditions and food processes compared to other microorganisms, elimination of these viruses by heat and high pressure applications, natural antiviral compounds, UV applications and conventional cleaning-disinfection remains difficult even inadequate. In protection from viral infections, vaccine applications together with GMP, GHP and HACCP system approaches in production seem to be the most effective approaches to ensure the minimization of viruses in food environment and in public. In this review article, up-to-date information is presented on the general characteristics and the diseases caused by enterotropic viruses; NoV, AstV, RoV, AdV and hepatotropic viruses; HAV and HEV, with a particularly high worldwide prevalence, as well as their epidemiology, prevention and their control measures.

scholarly journals MAIN TRENDS OF MONITORING OF VIRAL HEMORRHAGIC FEVERS ACTIVITY IN THE NATURAL FOCI

2018 ◽  
pp. 68-78
Author(s):  
Галина Компанец ◽  
Galina Kompanets
Keyword(s):  
Russian Federation ◽  
Viral Infections ◽  
Hemorrhagic Fever ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fevers ◽  
Innovative Methods ◽  
Viral Hemorrhagic Fevers ◽  
Natural Foci ◽  
Severe Fever

This paper includes review of innovative methods of monitoring of activity of natural foci of epidemically important for Russian Federation such viral infections as hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF), and the analysis of probability to control such «exotic» infections, as Denge fever and severe fever with thrombocytopenia syndrome (SFTS).

scholarly journals Innate Immune Responses to Highly Pathogenic Coronaviruses and Other Significant Respiratory Viral Infections

2020 ◽  
Vol 11 ◽  
Author(s):  
Hanaa Ahmed-Hassan ◽  
Brianna Sisson ◽  
Rajni Kant Shukla ◽  
Yasasvi Wijewantha ◽  
Nicholas T. Funderburg ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Highly Pathogenic ◽  
Respiratory Viral Infections

scholarly journals Nosocomial Transmission of Emerging Viruses via Aerosol-Generating Medical Procedures

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 940 ◽  
Author(s):  
Seth D. Judson ◽  
Vincent J. Munster
Keyword(s):  
Health Care ◽  
Ebola Virus ◽  
Viral Infections ◽  
Nipah Virus ◽  
Hemorrhagic Fever ◽  
Nosocomial Transmission ◽  
Medical Procedures ◽  
Emerging Viruses ◽  
Pathogenic Viruses ◽  
Infection Control Guidelines

Recent nosocomial transmission events of emerging and re-emerging viruses, including Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Crimean–Congo hemorrhagic fever orthonairovirus, have highlighted the risk of nosocomial transmission of emerging viruses in health-care settings. In particular, concerns and precautions have increased regarding the use of aerosol-generating medical procedures when treating patients with such viral infections. In spite of increasing associations between aerosol-generating medical procedures and the nosocomial transmission of viruses, we still have a poor understanding of the risks of specific procedures and viruses. In order to identify which aerosol-generating medical procedures and emerging viruses pose a high risk to health-care workers, we explore the mechanisms of aerosol-generating medical procedures, as well as the transmission pathways and characteristics of highly pathogenic viruses associated with nosocomial transmission. We then propose how research, both in clinical and experimental settings, could advance current infection control guidelines.

scholarly journals Differential Immune Responses to Hemorrhagic Fever-Causing Arenaviruses

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 138 ◽  
Author(s):  
Mantlo ◽  
Paessler ◽  
Huang
Keyword(s):  
Clinical Importance ◽  
Hemorrhagic Fever ◽  
Lassa Fever ◽  
Innate Immune ◽  
Host Immune System ◽  
Lassa Virus ◽  
Type I ◽  
Highly Pathogenic ◽  
The Family ◽  
Pro Inflammatory Cytokines

The family Arenaviridae contains several pathogens of major clinical importance. The Old World (OW) arenavirus Lassa virus is endemic in West Africa and is estimated to cause up to 300,000 infections each year. The New World (NW) arenaviruses Junín and Machupo periodically cause hemorrhagic fever outbreaks in South America. While these arenaviruses are highly pathogenic in humans, recent evidence indicates that pathogenic OW and NW arenaviruses interact with the host immune system differently, which may have differential impacts on viral pathogenesis. Severe Lassa fever cases are characterized by profound immunosuppression. In contrast, pathogenic NW arenavirus infections are accompanied by elevated levels of Type I interferon and pro-inflammatory cytokines. This review aims to summarize recent findings about interactions of these pathogenic arenaviruses with the innate immune machinery and the subsequent effects on adaptive immunity, which may inform the development of vaccines and therapeutics against arenavirus infections.

scholarly journals Obesity as a risk factor for dengue shock syndrome in children

2013 ◽  
Vol 53 (4) ◽  
pp. 187 ◽  
Author(s):  
Maria Mahdalena Tri Widiyati ◽  
Ida Safitri Laksanawati ◽  
Endy Paryanto Prawirohartono
Keyword(s):  
Risk Factor ◽  
Viral Infections ◽  
Infection Type ◽  
Secondary Infection ◽  
Univariate Analysis ◽  
Fluid Management ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Control Group ◽  
Case Group

Background Dengue hemorrhagic fever (DHF) leads to highmorbidity and mortality if not be treated properly and promptly.Obesity may play a role in the progression ofDHF to dengue shocksyndrome (DSS) and could be a prognostic factor.Objective To evaluate childhood obesity as a prognostic factorfor DSS.Methods We reviewed medical records of patients with DHFand DSS admitted to Department of Child Health, Dr. SardjitoHospital, Yogyakarta between June 2008 and February 2011.Subjects were aged less than 18 years and fulfilled WHO criteria(1997) for DHF or DSS. The exclusion criteria were the denguefever, a milder form of disease, or other viral infections. Riskfactors for DSS were analyzed by logistic regression analysis.Results Of342 patients who met the inclusion criteria, there were116 DSS patients (33 .9%) as the case group and 226 DHF patients(66.1%) as the control group. Univariate analysis revealed thatrisk factors for DSS were obesity (OR= 1.88; 95%CI 1.01 to3.5 l) ,secondary infection type (OR=0.82; 95%CI 0.41 to 1.63), plasmaleakage with hematocrit increase> 25% (OR=3.42; 95%CI 2.06to 5.65), platelet count < 20,000/μL (OR= l.95; 95%CI 1.20 to3 .16), and inadequate fluid management from prior hospitalization(OR=9.ll; 95% CI 1.13 to 73.66). By multivariate analysis,plasma leakage with hematocrit increase > 25% was associatedwith DSS (OR=2.5 l; 95%CI 1.12 to 5.59), while obesity was notassociated with DSS (OR= l.03; 95%CI 0.32 to3.3 1).Conclusion Obesity is not a risk factor for DSS, while plasmaleakage with hematocrit increase > 25% is associated with DSS.

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