EBOV
Etiology
Taxonomy
I Order = [[ Mononegavirales ]] I Family = [[ Filoviridae ]] I Genus = [[ Ebolavirus ]] I Species = [[ Zaire ebolavirus ]] I
Description
Pathogenesis
Transmission
There are two types of exposures that contribute to acquiring the Ebola virus. The first, primary exposure, is due to travel in an ebola endemic area. The second mode of transmission is contact with bodily fluids of an infected host. In addition, using unsterilized hospital equipment that came in contact with the virus.
Infectious dose and incubation
Upon invasion of host cells, the virus typically presents a 2-21 day incubation period. The infectious dose is very low; 1-10 aerosolized particles are sufficient to cause disease.
Epidemiology
Virulence Factors
VP35
Previous studies demonstrate VP35 is protein virulence factor that serves as a cofactor for viral RNA polymerase complex, RNAi silencing suppressor and for viral assembly. In addition, VP35 promotes immune lapse by antagonizing antiviral signaling pathways and by denaturing the type I IFN system. Thus, the protein is able to replicate RNA and evade host cells. EBOV VP35 IID interferes with type I interferons (IFNs) and IFNα/β upon the engagement of PRRs and PAMPs, which ultimately produce the necessary type I IFNs. Transcription factors (IRF)3, IRF-7, and NKκ stimulate the IFNα/β to release IFNα and IFNβ. IFNα and IFNβ in turn stimulate antiviral activity genes like MHC class I and PKR. By activating these genes, we can reduce viral replication and in turn reduce the spread of infection. Inhibition of IFNα/β indirectly affects dendritic cell maturation because IFN production is reduced.
The mechanism by which VP35 binds its RNA remains uncertain. However, structural studies of the protein reveal that it is comprised of two subdomains. The alpha subdomain is composed of a four helix bundle and the beta domain is composed of four antiparallel beta strands, alpha helix, and a polyproline helix. Furthermore, the VP35 contains two basic patches, one in the beta sheet subdomain and the other in the alpha helical subdomain. The beta sheet domain has Arg305, Arg12, and Lys309 that allow for further immune suppression. VP35 is also characterized by an “end cap” that is composed of hydrophobic Phe239 and Ile340; this hydrophobic area allows RNA to bind to VP35 IID; in turn, antagonize antiviral signaling pathways. The N-terminus of the protein is utilized to allow NP and VP40 binding, the formation of viral polymerase complex, PKR, and RNAi silencing suppression. Scientists believe that perhaps preventing the adherence of VP35, the ebola virus can be avoided completely.
GP
Clinical features
Symptoms
Viral infection is characterized by the onset of malaise, fever, myalgia, diarrhea, vomiting, and headaches. As the disease progresses, gastrointestinal bleeding, lymphopenia, neutrophilia, maculopapular rash, conjuctivitis, along with external bleeding may occur. Some patients are able to recover from the infection; however, it remains unknown as to why some recover and others fail. Infected individuals are quarantined in a facility that entails the necessary safety measures authored by the CDC and WHO. Health care professionals dress in biohazard suits before coming in contact with a patient. If biohazard suits are not available, protective clothing, goggles, gloves, and mask should be worn. Survivors are typically left with a range of maladies that include fatigue, bulimia, hearing loss, tinnitus, arthralgias, orchitis, and suppurative parotitis.
Mortality
Diagnosis
Typically, clinical diagnosis can only be made after the first few days of symptoms because the early symptoms could have been caused by many other factors. Laboratory tests such as, enzyme-linked immunosorbent assay (ELISA), serum neturalization tests, antigen detection tests, virus isolation ,and a reverse transcriptase polymerase chain reaction (RT-PCR) definitively allow the detection of the ebola virus in a patient. These tests are conducted under maximum biological containment conditions.
Treatment
Currently, vaccines and antivirals are not available to treat EBOV. Patients are provided supportive treatment that includes attention to: Replacement of fluids, electrolytes, constant monitoring of blood pressure and oxygen levels, nutrition and comfort.
Prevention
To reduce the risk of acquiring the Ebola virus, avoid travelling to endemic areas in Africa. In addition, avoid consuming bush meats that are sold on street markets. Wear gloves, protective clothing, and a mask when caring for an ill that may possibly be affect with ebola. Also avoid coming in contact with an infected corpse. Wash hands frequently when travelling; if no soap is available, rub hands with 60% alcohol. Take careful precautions before coming in contact with the fluids of non-human primates from Africa or the Philippines.
Host Immune Response
References
References
Created by {Bhumi Patel}, student of Tyrrell Conway at the University of Oklahoma.
