Pathophysiology and Clinical Features of Ebola Virus Infection
Joseph R. Masci, Elizabeth Bass in Ebola, 2017
The typical case of Ebola virus disease (EVD) begins with influenza-like features and culminates in the kind of cytokine storm described above. The clinical manifestations of EVD have been divided into three phases (Beeching et al. 2014). The first phase, typically lasting several days, consists of nonspecific findings, such as fever and muscle aches (Beeching et al. 2014), mimicking many other infectious diseases. The second phase typically includes gastrointestinal manifestations, particularly vomiting and diarrhea leading to dehydration. The third phase, usually beginning in the second week of illness, culminates in death or recovery and features vascular collapse and, in some cases, hemorrhagic and neurological complications. Hemorrhagic complications, with which filovirus infections such as EVD have been associated historically, were seen less frequently than expected in the 2014–2016 outbreaks. Fatal cases progress through an illness that resembles severe bacterial sepsis and septic shock, culminating in irreversible vascular collapse. In a series from Sierra Leone of 581 patients, those who died typically did so after 7–8 days of illness (Ansumana et al. 2015).
Arenaviruses and Neurovirology
Sunit K. Singh, Daniel Růžek in Neuroviral Infections, 2013
Laboratory rodents can be infected with the hemorrhagic fever arenaviruses experimentally but have not been found naturally infected. The infections, unlike with LCM, have not been observed in pet rodents, but it is conceivable that exposure to a potentially susceptible rodent may occur if an imported, infected, exotic rodent is exposed in a pet shop, animal “swap meet,” or distribution center to other species, as was observed in the monkeypox imported in the United States in the giant pouched Gambian rat and transmitted to American prairie dogs that were subsequently sold as pets (Reed et al. 2004). A non-mammal arenavirus-like pathogen has recently been described in snakes associated with inclusion body disease (Stenglein et al. 2012). This multisystem disease causes behavioral changes in the snakes and, intestingly, has some characteristics of filoviruses as well.
Order Mononegavirales
Paul Pumpens, Peter Pushko, Philippe Le Mercier in Virus-Like Particles, 2022
The filoviruses also have a long and successful history of the use of their glycoproteins as pseudotyping agents. First, the pseudotyped lentiviral vectors were constructed for the delivery of lentiviral vectors to the cells exposing receptors for the filoviruses, for example, folate receptor alpha, a glycosylphosphatidylinositol-linked surface protein on the apical surface of airway epithelia (Kobinger et al. 2001; Medina et al. 2003; Sinn et al. 2003). Another retroviral vector, namely the MLV vector, was used to construct cross protective filoviral vaccine candidates based on the retro-VLPs that were pseudotyped by the EBOV GP lacking mucin-like domain or on the appropriate DNA plasmids, or so-called plasmo-retro VLPs able to direct production of retro-VLPs (Ou et al. 2012).
Small animal models of filovirus disease: recent advances and future directions
Published in Expert Opinion on Drug Discovery, 2018
Robert W. Cross, Karla A. Fenton, Thomas W. Geisbert
Since their discovery in 1967, filoviruses have been the source of many outbreaks of severe viral hemorrhagic fever (VHF) throughout the world [1]. Members of the Filoviridae family responsible for these outbreaks belong to both the Ebolavirus and Marburgvirus genera [1]. These viruses have rightfully garnered much attention due to the rapid and severe disease course associated with elevated communicability and case fatality rates (CFR) of up to 90% in humans and nonhuman primates (NHP). Filoviruses require Biosafety Level (BSL)-4 laboratory containment for handling due to their highly infectious nature, elevated CFR, and lack of approved medical countermeasures (MCM) which also has warranted their classification as Tier 1 Select Agents in the USA [2]. Recently, the World Health Organization has listed both ebolaviruses and marburgviruses as emerging threats most likely to cause major epidemics and thus should be considered among the highest priorities for development of MCMs [3].
Defibrotide: potential for treating endothelial dysfunction related to viral and post-infectious syndromes
Published in Expert Opinion on Therapeutic Targets, 2021
Edward Richardson, David García-Bernal, Eleonora Calabretta, Rubén Jara, Marta Palomo, Rebecca M. Baron, Gregory Yanik, Jawed Fareed, Israel Vlodavsky, Massimo Iacobelli, Maribel Díaz-Ricart, Paul G. Richardson, Carmelo Carlo-Stella, Jose M. Moraleda
Viral hemorrhagic fevers are caused by four families of RNA viruses: arenaviruses, bunyaviruses, filoviruses, and flaviviruses. These viruses have diverse pathogenic mechanisms, resulting in varying disease severity and presentation [62]. The Ebola virus, a filovirus, accounts for few infections annually but stands among the most lethal viruses known, with reported fatality rates ranging from 24% to 100% in different outbreaks [63]. Dengue virus, a flavivirus, accounts for an estimated 390 million infections per year, of which only 96 million manifests with disease symptoms [64]. Hantavirus, a bunyavirus, manifests itself as two hemorrhagic febrile diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) [65]. While these diseases differ in severity, incidence, and presentation, their severe manifestations share features of vascular instability, hemorrhage, and cytokine storm [62]. These viruses are noteworthy, furthermore, for their interaction with ECs, such as Ebola virus, dengue virus, and Hantavirus each directly infect ECs in the course of disease pathogenesis [66–68].
Targeting Ebola virus replication through pharmaceutical intervention
Published in Expert Opinion on Investigational Drugs, 2021
Frederick Hansen, Heinz Feldmann, Michael A Jarvis
Over the next years, the field needs to prioritize refinement of current promising approaches and move them through clinical trials for licensure application. Those drugs (or combinations thereof) then need to be produced to sufficient quantities and properly stored for immediate and uncomplicated release and administration. With lower priority, second-generation drug development programs should continue as needed and funding allows. If the COVID-19 pandemic has taught us anything, it is that preemption is by far less costly in lives and resources than reaction with poor preparation. Finally, early and rapid diagnosis in combination with immediate isolation of cases and thorough contact tracing cannot be replaced by any therapeutic intervention. These public health measures are a necessary prerequisite for any successful therapeutic intervention strategy in future filovirus outbreaks.
Related Knowledge Centers
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