scholarly journals Can Ebola Virus evolve to be less virulent in humans?

2017 ◽  
Author(s):  
Mircea T. Sofonea ◽  
Lafi Aldakak ◽  
Luis Fernando Boullosa ◽  
Samuel Alizon
Keyword(s):  
Public Health ◽  
Life Cycle ◽  
Ebola Virus ◽  
Evolutionary Dynamics ◽  
Case Fatality ◽  
Sexual Contact ◽  
Selection For ◽  
Dead Bodies ◽  
Regular Contact

AbstractThis preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (<http://dx.doi.org/10.24072/pci.evolbiol.100022>). Understanding Ebola Virus (EBOV) virulence evolution is not only timely but also raises specific questions because it causes one of the most virulent human infections and it is capable of transmission after the death of its host. Using a compartmental epidemiological model that captures three transmission routes (by regular contact, via dead bodies and by sexual contact), we infer the evolutionary dynamics of case fatality ratio (CFR) on the scale of an outbreak and on the long term. Our major finding is that the virus’s specific life cycle imposes selection for high levels of virulence and that this pattern is robust to parameter variations in biological ranges. In addition to shedding a new light on the ultimate causes of EBOV’s high virulence, these results generate testable predictions and contribute to informing public health policies. In particular, burial management stands out as the most appropriate intervention since it decreases the R0 of the epidemics, while imposing selection for less virulent strains.Impact SummaryThe severe haemorrhagic fever caused by Ebola Virus (EBOV) usually kills more than one infected individual out of two in the absence of treatment, which makes this pathogen one of the most virulent known to humans. The recent outbreak in West Africa (2013-2016) revealed that the virus is able to spread and persist for months across countries. It is often thought that virulence could be due to the fact that the virus is adapted to its reservoir host. Given that microbes evolve rapidly, it is important to determine whether EBOV virulence is likely to decrease as the virus adapts to its human host. To address this problem, we developed a novel mathematical model tailored to EBOV’s life cycle, notably by capturing its three main transmission routes (by regular contact, sexual contact and via dead bodies). We investigated the evolutionary trends of EBOV’s virulence on different time scales (outbreak initiation, short term and long term). Our results reveal that the virulence of EBOV might not be due to the maladaptation of the virus, but could rather originate from its unique life cycle. These results are robust to the parameter values chosen. From a public health perspective, burial management stands out as the main leverage to fight the virulence of EBOV, both on the short and long terms.

scholarly journals Differences in Viral RNA Synthesis but Not Budding or Entry Contribute to the In Vitro Attenuation of Reston Virus Compared to Ebola Virus

2020 ◽  
Vol 8 (8) ◽  
pp. 1215
Author(s):  
Bianca S. Bodmer ◽  
Josephin Greßler ◽  
Marie L. Schmidt ◽  
Julia Holzerland ◽  
Janine Brandt ◽  
...  
Keyword(s):  
Life Cycle ◽  
Rna Synthesis ◽  
Ebola Virus ◽  
Severe Disease ◽  
Case Fatality ◽  
Viral Rna ◽  
Pathogenic Potential ◽  
Rnp Complex ◽  
Reston Virus

Most filoviruses cause severe disease in humans. For example, Ebola virus (EBOV) is responsible for the two most extensive outbreaks of filovirus disease to date, with case fatality rates of 66% and 40%, respectively. In contrast, Reston virus (RESTV) is apparently apathogenic in humans, and while transmission of RESTV from domestic pigs to people results in seroconversion, no signs of disease have been reported in such cases. The determinants leading to these differences in pathogenicity are not well understood, but such information is needed in order to better evaluate the risks posed by the repeated spillover of RESTV into the human population and to perform risk assessments for newly emerging filoviruses with unknown pathogenic potential. Interestingly, RESTV and EBOV already show marked differences in their growth in vitro, with RESTV growing slower and reaching lower end titers. In order to understand the basis for this in vitro attenuation of RESTV, we used various life cycle modeling systems mimicking different aspects of the virus life cycle. Our results showed that viral RNA synthesis was markedly slower when using the ribonucleoprotein (RNP) components from RESTV, rather than those for EBOV. In contrast, the kinetics of budding and entry were indistinguishable between these two viruses. These data contribute to our understanding of the molecular basis for filovirus pathogenicity by showing that it is primarily differences in the robustness of RNA synthesis by the viral RNP complex that are responsible for the impaired growth of RESTV in tissue culture.

scholarly journals Persistence and Sexual Transmission of Filoviruses

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 683 ◽  
Author(s):  
Brayden G. Schindell ◽  
Andrew L. Webb ◽  
Jason Kindrachuk
Keyword(s):  
Public Health ◽  
Ebola Virus ◽  
Reproductive Tract ◽  
Virus Disease ◽  
Sexual Transmission ◽  
Viral Persistence ◽  
Asymptomatic Infection ◽  
Global Public Health ◽  
Geographic Regions

There is an increasing frequency of reports regarding the persistence of the Ebola virus (EBOV) in Ebola virus disease (EVD) survivors. During the 2014–2016 West African EVD epidemic, sporadic transmission events resulted in the initiation of new chains of human-to-human transmission. Multiple reports strongly suggest that these re-emergences were linked to persistent EBOV infections and included sexual transmission from EVD survivors. Asymptomatic infection and long-term viral persistence in EVD survivors could result in incidental introductions of the Ebola virus in new geographic regions and raise important national and local public health concerns. Alarmingly, although the persistence of filoviruses and their potential for sexual transmission have been documented since the emergence of such viruses in 1967, there is limited knowledge regarding the events that result in filovirus transmission to, and persistence within, the male reproductive tract. Asymptomatic infection and long-term viral persistence in male EVD survivors could lead to incidental transfer of EBOV to new geographic regions, thereby generating widespread outbreaks that constitute a significant threat to national and global public health. Here, we review filovirus testicular persistence and discuss the current state of knowledge regarding the rates of persistence in male survivors, and mechanisms underlying reproductive tract localization and sexual transmission.

scholarly journals Extraordinary long-term and fluctuating persistence of Ebola virus RNA in semen of survivors in Guinea: implications for public health

2017 ◽  
Vol 23 (6) ◽  
pp. 412-413 ◽  
Author(s):  
A.K. Keita ◽  
A. Toure ◽  
M.S. Sow ◽  
H. Raoul ◽  
N'F. Magassouba ◽  
...  
Keyword(s):  
Public Health ◽  
Ebola Virus ◽  
Virus Rna

scholarly journals The Cellular Protein CAD is Recruited into Ebola Virus Inclusion Bodies by the Nucleoprotein NP to Facilitate Genome Replication and Transcription

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1126 ◽  
Author(s):  
Janine Brandt ◽  
Lisa Wendt ◽  
Bianca S. Bodmer ◽  
Thomas C. Mettenleiter ◽  
Thomas Hoenen
Keyword(s):  
Life Cycle ◽  
Host Cell ◽  
Inclusion Bodies ◽  
Ebola Virus ◽  
Case Fatality ◽  
Host Factor ◽  
Genome Replication ◽  
Carbamoyl Phosphate ◽  
Aspartate Transcarbamylase ◽  
A Genome

Ebola virus (EBOV) is a zoonotic pathogen causing severe hemorrhagic fevers in humans and non-human primates with high case fatality rates. In recent years, the number and extent of outbreaks has increased, highlighting the importance of better understanding the molecular aspects of EBOV infection and host cell interactions to control this virus more efficiently. Many viruses, including EBOV, have been shown to recruit host proteins for different viral processes. Based on a genome-wide siRNA screen, we recently identified the cellular host factor carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) as being involved in EBOV RNA synthesis. However, mechanistic details of how this host factor plays a role in the EBOV life cycle remain elusive. In this study, we analyzed the functional and molecular interactions between EBOV and CAD. To this end, we used siRNA knockdowns in combination with various reverse genetics-based life cycle modelling systems and additionally performed co-immunoprecipitation and co-immunofluorescence assays to investigate the influence of CAD on individual aspects of the EBOV life cycle and to characterize the interactions of CAD with viral proteins. Following this approach, we could demonstrate that CAD directly interacts with the EBOV nucleoprotein NP, and that NP is sufficient to recruit CAD into inclusion bodies dependent on the glutaminase (GLN) domain of CAD. Further, siRNA knockdown experiments indicated that CAD is important for both viral genome replication and transcription, while substrate rescue experiments showed that the function of CAD in pyrimidine synthesis is indeed required for those processes. Together, this suggests that NP recruits CAD into inclusion bodies via its GLN domain in order to provide pyrimidines for EBOV genome replication and transcription. These results define a novel mechanism by which EBOV hijacks host cell pathways in order to facilitate genome replication and transcription and provide a further basis for the development of host-directed broad-spectrum antivirals.

The Long-Term Periodic Patterns of Global Rabies Epidemics Among Animals: A Modeling Analysis

2020 ◽  
Vol 30 (03) ◽  
pp. 2050047
Author(s):  
Salihu Sabiu Musa ◽  
Shi Zhao ◽  
Daihai He ◽  
Chao Liu
Keyword(s):  
Public Health ◽  
Wavelet Analysis ◽  
Case Fatality Rate ◽  
Compartmental Model ◽  
Case Fatality ◽  
Transmission Dynamics ◽  
Fatality Rate ◽  
Periodic Patterns ◽  
Modeling Analysis

Rabies remains a serious threat to public health in Asia, Africa and some parts of Europe with a case fatality rate of 95%. We adopted wavelet analysis to study the long-term recurrence of global rabies outbreaks and found that a 3- to 4-year periodicity has existed since 2005. Furthermore, a simple compartmental model is developed and analyzed to study the transmission dynamics, and to show the existence of the observed periodicity as well as the endemic feature of rabies among animals. Our findings indicate the existence of the oscillation patterns (recurrence), and the epidemic is at its peak since 2018.

Strengthening of occupational health promotion by the German Prevention Health Care Act

2019 ◽  
pp. 188-190
Author(s):  
Diana Hart
Keyword(s):  
Public Health ◽  
Health Care ◽  
Health Promotion ◽  
Primary Prevention ◽  
Occupational Health ◽  
Life Expectancy ◽  
Prevention And Control ◽  
Occupational Health Promotion ◽  
And Control

All countries are faced with the problem of the prevention and control of non-communicable diseases (NCD): implement prevention strategies eff ectively, keep up the momentum with long term benefi ts at the individual and the population level, at the same time tackling hea lth inequalities. Th e aff ordability of therapy and care including innovative therapies is going to be one of the key public health priorities in the years to come. Germany has taken in the prevention and control of NCDs. Germany’s health system has a long history of guaranteeing access to high-quality treatment through universal health care coverage. Th r ough their membership people are entitled to prevention and care services maintaining and restoring their health as well as long term follow-up. Like in many other countries general life expectancy has been increasing steadily in Germany. Currently, the average life expectancy is 83 and 79 years in women and men, respectively. Th e other side of the coin is that population aging is strongly associated with a growing burden of disease from NCDs. Already over 70 percent of all deaths in Germany are caused by four disease entities: cardiovascular disease, cancer, chronic respiratory disease and diabetes. Th ese diseases all share four common risk factors: smoking, alcohol abuse, lack of physical activity and overweight. At the same time, more and more people become long term survivors of disease due to improved therapy and care. Th e German Government and public health decision makers are aware of the need for action and have responded by initiating and implementing a wide spectrum of activities. One instrument by strengthening primary prevention is the Prevention Health Care Act. Its overarching aim is to prevent NCDs before they can manifest themselves by strengthening primary prevention and health promotion in diff erent sett ings. One of the main emphasis of the Prevention Health Care Act is the occupational health promotion at the workplace.

EPEGENTIC TOXICOLOGY: PERSPECTIVES OF THE DEVELOPMENT

2018 ◽  
pp. 2-7
Author(s):  
G. A. Sofronov ◽  
E. L. Patkin
Keyword(s):  
Public Health ◽  
Life Cycle ◽  
Human Health ◽  
Chronic Exposure ◽  
Environmental Pollutants ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Mechanism Of Formation ◽  
Health Disorders ◽  
Time Periods

One of the complex problems of modern experimental toxicology remains the molecular mechanism of formation of human health disorders separated at different time periods from acute or chronic exposure to toxic environmental pollutants (ecotoxicants). Identifying and understanding what epigenetic changes are induced by the environment, and how they can lead to unfavorable outcome, are vital for protecting public health. Therefore, we consider it important a modern understanding of epigenetic mechanisms involved in the life cycle of mammals and assess available data on the environmentally caused epigenetic toxicity and, accordingly fledging epigenenomic (epigenetic) regulatory toxicology.

Long-term Piloting Of Osmotic MBR For Potable Reuse: Performance, Life-Cycle Assessment, and Lessons Learned

2016 ◽  
Vol 2016 (14) ◽  
pp. 830-854
Author(s):  
Tzahi Y Cath ◽  
Ryan W Holloway ◽  
Leslie Miller-Robbie ◽  
Mehul Patel ◽  
Jennifer R Stokes ◽  
...  
Keyword(s):  
Life Cycle Assessment ◽  
Life Cycle ◽  
Lessons Learned ◽  
Potable Reuse
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