scholarly journals SARS-CoV-2 B.1.1.7 Infection of Syrian Hamster Does Not Cause More Severe Disease, and Naturally Acquired Immunity Confers Protection

mSphere ◽  
2021 ◽  
Author(s):  
Ivette A. Nuñez ◽  
Christopher Z. Lien ◽  
Prabhuanand Selvaraj ◽  
Charles B. Stauft ◽  
Shufeng Liu ◽  
...  
Keyword(s):  
Animal Models ◽  
Syrian Hamster ◽  
Severe Disease ◽  
Mortality Rates ◽  
Viral Fitness ◽  
Acquired Immunity ◽  
Complete Protection ◽  
Enhanced Transmission ◽  
Prior Infection ◽  
Rapid Emergence

The rapid emergence of several variants of concern of SARS-CoV-2 calls for evaluations of viral fitness and pathogenicity in animal models in order to understand the mechanism of enhanced transmission and the possible increases in morbidity and mortality rates. Here, we demonstrated that immunity naturally acquired through a prior infection with the first-wave variant does confer nearly complete protection against the B.1.1.7 variant in Syrian hamsters upon reexposure.

scholarly journals Rapid isolation and resolution immune evasion and viral fitness across contemporary SARS-CoV-2 variants

2022 ◽  
Author(s):  
Anupriya Aggarwal ◽  
Alberto Stella ◽  
Anouschka Akerman ◽  
Gregory Walker ◽  
Vanessa Milogiannakis ◽  
...  
Keyword(s):  
Mortality Rates ◽  
Viral Fitness ◽  
Neutralising Antibodies ◽  
Viral Isolation ◽  
Rapid Isolation ◽  
The World ◽  
Developed World ◽  
Late Stages ◽  
Rapid Emergence ◽  
Roll Out

Abstract From late 2020 the world observed the rapid emergence of many distinct SARS-CoV-2 variants. At the same time, pandemic responses coalesced into significant global vaccine roll-out that have now significantly lowered Covid-19 hospital and mortality rates in the developed world. Over this period, we developed a rapid platform (R-20) for viral isolation and characterisation using primary remnant diagnostic swabs. This combined with quarantine testing and genomics surveillance, enabled the rapid isolation and characterisation of all major SARS-CoV-2 variants (all variants of concern and 6 variants of interest) globally with a 4-month period. This platform facilitated viral variant isolation and enabled rapid resolution of variant phenotype by allowing determining end point viral titers from primary nasopharyngeal swabs and through ranking of evasion of neutralising antibodies. In late 2021, when the Delta variant was dominating, Omicron rapidly emerged. Using this platform, we isolated and tested the first cases of this variant within Australia. In this setting we observed Omicron to diverge from other variants at two levels: Firstly, it ranks at the mots evasive to neutralisation antibodies compared to all VOCs and major VUIs. Secondly, it no longer engages TMPRSS2 during the late stages of fusion.

scholarly journals Marburg virus pathogenesis – differences and similarities in humans and animal models

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Kyle Shifflett ◽  
Andrea Marzi
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Virus Disease ◽  
Severe Disease ◽  
Mortality Rates ◽  
Marburg Virus ◽  
Highly Pathogenic ◽  
Pathogenic Virus ◽  
Field Efficacy ◽  
Efficacy Studies

AbstractMarburg virus (MARV) is a highly pathogenic virus associated with severe disease and mortality rates as high as 90%. Outbreaks of MARV are sporadic, deadly, and often characterized by a lack of resources and facilities to diagnose and treat patients. There are currently no approved vaccines or treatments, and the chaotic and infrequent nature of outbreaks, among other factors, makes testing new countermeasures during outbreaks ethically and logistically challenging. Without field efficacy studies, researchers must rely on animal models of MARV infection to assess the efficacy of vaccines and treatments, with the limitations being the accuracy of the animal model in recapitulating human pathogenesis. This review will compare various animal models to the available descriptions of human pathogenesis and aims to evaluate their effectiveness in modeling important aspects of Marburg virus disease.

Lost in post-translational modification—Dengue virus writes its own sequel

2021 ◽  
Vol 6 (61) ◽  
pp. eabk1555
Author(s):  
Soumya S. Yandamuri ◽  
Kevin C. O’Connor
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Severe Disease ◽  
Post Translational Modification ◽  
Dengue Virus Infection ◽  
Elevated Frequency ◽  
Prior Infection

Elevated frequency of afucosylated IgG1 antibodies during dengue virus infection is associated with prior infection and predicts severe disease.

scholarly journals Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Kathrin Becker ◽  
Georg Beythien ◽  
Nicole de Buhr ◽  
Stephanie Stanelle-Bertram ◽  
Berfin Tuku ◽  
...  
Keyword(s):  
Animal Models ◽  
Syrian Hamster ◽  
Neutrophil Extracellular Traps ◽  
Virus Antigen ◽  
Endothelial Damage ◽  
Vascular Lesions ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Pulmonary Lesions ◽  
Extracellular Traps

Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs in COVID-19 pathogenesis are needed. SARS-CoV-2 infection causes infection and interstitial pneumonia of varying severity in humans and COVID-19 models. Pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in COVID-19 patients. Furthermore, neutrophil extracellular traps (NETs), which are known to contribute to vessel inflammation or endothelial damage, have also been shown as potential driver of COVID-19 in humans. Though most studies in animal models describe the pulmonary lesions characterized by interstitial inflammation, type II pneumocyte hyperplasia, edema, fibrin formation and infiltration of macrophages and neutrophils, detailed pathological description of vascular lesions or NETs in COVID-19 animal models are lacking so far. Here we report different types of pulmonary vascular lesions in the golden Syrian hamster model of COVID-19. Vascular lesions included endothelialitis and vasculitis at 3 and 6 days post infection (dpi), and were almost nearly resolved at 14 dpi. Importantly, virus antigen was present in pulmonary lesions, but lacking in vascular alterations. In good correlation to these data, NETs were detected in the lungs of infected animals at 3 and 6 dpi. Hence, the Syrian hamster seems to represent a useful model to further investigate the role of vascular lesions and NETs in COVID-19 pathogenesis.

scholarly journals N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2

2021 ◽  
Author(s):  
Christopher M Weiss ◽  
Hongwei Liu ◽  
Erin E Ball ◽  
Samuel Lam ◽  
Tomas Hode ◽  
...  
Keyword(s):  
Immune Responses ◽  
Infectious Virus ◽  
Severe Disease ◽  
Upper Airway ◽  
Innate Immune ◽  
Morbidity And Mortality ◽  
Vaccine Hesitancy ◽  
Innate Immune Responses ◽  
Before And After ◽  
Rapid Emergence

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in more than 4 million deaths in the 20 months since the virus was discovered. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout and vaccine hesitancy. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N-dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of β-0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans. We tested GC as a potential countermeasure for COVID-19. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway and lungs. Our findings demonstrate a new application for soluble immunoadjuvants like GC for preventing severe disease associated with SARS-CoV-2.

Simulating Dictyocaulus viviparus infection in calves: the parasitic phase

Parasitology ◽  
2000 ◽  
Vol 120 (7) ◽  
pp. 3-15 ◽  
Author(s):  
H. W. PLOEGER ◽  
M. EYSKER
Keyword(s):  
Model Simulation ◽  
Current Model ◽  
Mortality Rates ◽  
Development Rate ◽  
Model Description ◽  
Acquired Immunity ◽  
Dictyocaulus Viviparus ◽  
Improve Model ◽  
Juvenile Stages ◽  
Parasitic Phase

A model simulating Dictyocaulus viviparus infection in calves is described. The present paper only deals with the parasitic phase of the life-cycle. Descriptions are given for establishment, development rate of juvenile stages, mortality rates of both juvenile and adult stages, and fecundity. Literature data were used to to develop parameter functions and to estimate initial values for constants. Development of acquired immunity, defined as the proportional ability of the host to reduce the number of parasite individuals in some stage or about to move into a next stage, against establishment (protection) or affecting mortality rates of juvenile or adult parasite stages has been included. The effect of immunity on one parameter or process is viewed as distinctly separate from the effect on another. Preliminary comparisons between model prediction and observations gives encouraging results, indicating that the model simulates experimental D. viviparus infection in calves reasonably well. Some quantitative discrepancies between prediction and observation make clear however, that not all parts of the model are accurate. Further experimentation is needed to re-evaluate current model description and to improve model simulation.

scholarly journals Immune Modulation and Immune-Mediated Pathogenesis of Emerging Tickborne Banyangviruses

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 125 ◽  
Author(s):  
Mendoza ◽  
Ebihara ◽  
Yamaoka
Keyword(s):  
Immune Modulation ◽  
Severe Disease ◽  
Hemorrhagic Fever ◽  
Mortality Rates ◽  
Viral Hemorrhagic Fever ◽  
New Class ◽  
Viral Immune Evasion ◽  
Immune Mediated ◽  
Significant Disease ◽  
Severe Fever

In the last decade, the emergence of several, novel tickborne viruses have caused significant disease in humans. Of interest are the tickborne banyangviruses: Severe fever with thrombocytopenia syndrome virus (SFTSV), Heartland virus (HRTV), and Guertu virus (GTV). SFTSV and HRTV infection in humans cause viral hemorrhagic fever-like disease leading to mortality rates ranging from 6–30% of the cases. The systemic inflammatory response syndrome (SIRS) associated with SFTSV infection is hypothesized to contribute significantly to pathology seen in patients. Despite the severe disease caused by HRTV and SFTSV, there are no approved therapeutics or vaccines. Investigation of the immune response during and following infection is critical to the generation of fully protective vaccines and/or supportive treatments, and overall understanding of viral immune evasion mechanisms may aid in the development of a new class of therapeutics.

scholarly journals Right Ventricle Remodeling and Function in Scleroderma Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Roxana Cucuruzac ◽  
Iolanda Muntean ◽  
Imre Benedek ◽  
Andras Mester ◽  
Nora Rat ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Severe Disease ◽  
Mortality Rates ◽  
Pulmonary Artery Hypertension ◽  
Organ Manifestations ◽  
Therapeutic Measures ◽  
The One ◽  
And Function ◽  
Adaptive Pattern ◽  
Functional Alteration

Scleroderma, known also as systemic sclerosis (SSc), is a severe disease associated with high mortality rates, and right ventricular (RV) remodeling and dysfunction, along with pulmonary artery hypertension (PAH), are among the most important internal organ manifestations of this disease. PAH has a higher prevalence in patients with SSc compared to the general population and represents a significant predictor of mortality in SSc. In patients with SSc, the morphological remodeling and alteration of RV function begin even before the setting of PAH and lead to development of a specific adaptive pattern of the RV which is different from the one recorded in patients with IAPH. These alterations cause worse outcomes and increased mortality rates in SSc patients. Early detection of RV dysfunction and remodeling is possible using modern imaging tools currently available and can indicate the initiation of specific therapeutic measures before installation of PAH. The aim of this review is to summarize the current knowledge related to mechanisms involved in the remodeling and functional alteration of the RV in SSc patients.

scholarly journals Acquired Immunity to Malaria

2009 ◽  
Vol 22 (1) ◽  
pp. 13-36 ◽  
Author(s):  
Denise L. Doolan ◽  
Carlota Dobaño ◽  
J. Kevin Baird
Keyword(s):  
Plasmodium Falciparum ◽  
High Risk ◽  
Immune Status ◽  
Severe Disease ◽  
Sub Saharan Africa ◽  
Acquired Immunity ◽  
Sub Saharan ◽  
High Risk Infants ◽  
Induced Immunity ◽  
Infants And Young Children

SUMMARY Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection. This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. We advocate that naturally acquired immunity should be appreciated as being virtually 100% effective against severe disease and death among heavily exposed adults. Even the immunity that occurs in exposed infants may exceed 90% effectiveness. The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity.

scholarly journals A60 Revealing the evolution of virulence in RNA viruses

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Marina Escalera-Zamudio ◽  
Bernardo Gutiérrez ◽  
Julien Thézé ◽  
Oliver G Pybus
Keyword(s):  
Influenza A ◽  
Hepatitis A Virus ◽  
Rna Viruses ◽  
Phenotypic Diversity ◽  
Severe Disease ◽  
Protein Structures ◽  
Viral Fitness ◽  
Lassa Virus ◽  
Virulence Determinants ◽  
New Host

Abstract A combination of high rates of mutation and replication, coupled with strong natural selection, ensures that RNA viruses experience rapid genotypic and phenotypic evolution. Such a ‘fast-forward’ evolution enables viruses to rapidly adapt to new host species, evade host immune responses, and to develop resistance to anti-viral drugs. Similarly, rapid evolution allows viruses to attain new levels of virulence, defined as the ability to cause severe disease in hosts. We hypothesize that distinct viral groups share genetic determinants that modulate virulence that have been acquired through convergent evolution. Thus, common patterns reflecting changing virulence-related specific viral groups could be detected. The main goals for this project are (1) to understand how genetic and phenotypic diversity can be generated among different viral groups by analyzing the variation patterns and determining the selective forces behind them (impact in viral fitness) and (2) to understand how fixed mutations can modulate virulence within different viral groups by performing comparison of strains with differing virulence within a longitudinal timescale. The subject of the study is key emerging and re-emerging virus families of medical importance. Such groups include: Coronaviridae (severe acute respiratory syndrome and Middle East respiratory syndrome-associated coronaviruses), Picornaviridae (Hepatitis A virus), Flaviviridae (Yellow fever, West Nile, Hepatitis C, Dengue, and Zika viruses), Togaviridae (Rubella and Chikungunya virus), Bornaviridae (Borna-disease virus), Filoviridae (Ebola and Marburg viruses), Paramyxoviridae (Measles, Nipah, and Hendra viruses), Rhabdoviridae (Lyssaviruses), Arenaviridae (Lassa virus), Bunyaviridae (Hanta- and Crimean-Congo hemorrhagic fever viruses), and Orthomyxoviridae (Influenza A viruses). Viral genomes collected at different time points, different hosts (human and their most closely related animal reservoirs) and different locations will be compiled. Extensive molecular evolutionary analyses will be carried out to infer gene expansion/contraction within groups, rates of evolution, and changes in selection pressure, including the detection of positive selected genes and sites (adaptive evolution). Positively selected sites will be mapped onto the viral protein structures to reveal their impact on function, and hence the location of potential virulence determinants. Virulence changes among particular viral strains and types will be defined and measured according to definitions based on an increase in: (1) transmissibility, (2) host tropism, (3) immune evasion, (4) morbidity and mortality, (5) drug resistance, and by the incorporation of epidemiological data to determine whether high or low virulence strains within different hosts and localities are spreading most efficiently in nature.

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