Rabies, Marburg, & Ebola Viruses
Sections
Rhabdoviruses & Filoviruses
Key Features
Enveloped, single-stranded negative-sense RNA viruses that form helical nucleocapsids.
The pathogenic viruses that we'll learn about in this tutorial are zoonotic.
Rhabdoviruses: Rabies
Rod-shaped; "rhabdo" means "rod."
Genome encodes only 5 genes.
Helical nucleocapsid gives the virion a striated appearance under electron microscope.
Lyssavirus genus includes Rabies and Rabies-like viruses**
Filoviruses: Hemorrhagic fever
Formerly included in the Rhabdoviridae.
Pleomorphic; appear as long, short, or branched filaments.
Marburg virus and Ebola virus are key pathogenic viruses that cause hemorrhagic fever.
Rabies virus
Causes an acute, fatal nervous system infection.
General pathogenesis:
- Viral inoculation: The virus is most often transmitted via a bite or scratch from an infected animal
Infection in animals produces aggressive behavior that promotes transmission via bites or scratches.
More rarely, aerosolized virions are inhaled or the virus is obtained from infected tissue transplants.
Worldwide, unvaccinated dogs are the major sources of human rabies infections.
Because of widespread canine vaccination programs in the United States, cats and undomesticated carnivores (raccoons, bats, etc.) are the primary reservoirs.
- Replication in local muscle tissue; or, the virus can enter the peripheral nervous system, directly.
- Retrograde axonal transport. Upon entering peripheral nerves, the virus uses retrograde axonal transport to reach the central nervous system. Current research suggests that rabies virions bind with acetylcholine receptors, neural cell adhesion molecules (NCAM), and other neural receptors.
- Replication in dorsal ganglions.
- Ascension to structures in the brain and brainstem.
- CNS infection & replication. Rabies virus infects and replicates within central nervous structures, which can produce encephalitis.
Histopathologic evidence:
Negri bodies are cytoplasmic inclusion bodies that contain viral proteins and RNA. Be aware that the presence of Negri bodies is variable, and, that they are especially found in the pyramidal cells of the hippocampus (specifically, in Ammon's horn) and in Purkinje cells of the cerebellum.
Perivascular cuffing occurs when the virus triggers inflammatory cell accumulation around blood vessels.
- Virus descends to infect the skin, glands, and other organs. The virus specifically travels to and infects the salivary glands.
In non-human animals, migration to the salivary glands is key for transmission via saliva.
5 stages of rabies virus infection in humans
- Incubation stage. Typically lasts 1-3 months, but is highly variable, and can last much longer.
– Duration of the incubation period is related to the distance between the inoculation site and the CNS, as well as host and viral factors.
- Prodrome stage lasts for 2-10 days, and is marked by the appearance of nonspecific symptoms and tingling or pain at the wound site. Some patients experience respiratory, gastrointestinal, or central nervous symptoms.
- Neurologic stage is characterized by symptoms of "furious" and/or "paralytic" rabies:
Furious, aka, encephalitic rabies = Hyperactivity (agitation, mania) and hydrophobia. Hydrophobia, which is fear or avoidance of water, is attributed to painful spasms of the pharyngeal muscles used for swallowing.
Paralytic, aka, "dumb" rabies = Flaccid paralysis. Patients with these symptoms are often misdiagnosed.
The end of this phase is marked by irregular, rapid breathing.
- Coma.
- Death due to cardio-respiratory arrest.
Very few survive rabies infection without prompt immunization.
Treatment and Prevention
Best prevented via widespread canine and other animal vaccination programs.
At-risk humans, such as veterinary or lab workers, can receive pre-exposure immunization.
Fatal without vaccination prior to the appearance of neurologic symptoms.
Filoviruses: Marburg Virus and Ebola Virus
African origins.
Reservoirs are uncertain; recent research suggests that bats are important reservoirs.
Filoviruses dysregulate host inflammatory responses and promote inflammation. This alloww for uncontrolled replication.
High mortality rates.
Can be transmitted from human to human; thus, caretakers are at significant risk of infection.
Pathogenesis:
Marburg and Ebola virus infections produce hemorrhagic fever with liver and kidney damage
– Vomiting and diarrhea rapidly progress to disseminated intravascular coagulation, shock, and, in many cases, death.
Gastrointestinal hemorrhaging and organ necrosis is common; potential for neurologic complications.
Treatment & Prevention
Viral hemorrhagic fever isolation precautions (aka, barrier nursing).
No specific treatment. Supportive care includes fluid and electrolyte replenishment (to counter diarrhea and vomiting) and, when needed, blood pressure maintenance (to avoid shock).
References
Rabies:
Beck, S., P. Gunawardena, D. L. Horton, D. J. Hicks, D. A. Marston, A. Ortiz-Pelaez, A. R. Fooks, and A. Núñez. "Pathobiological Investigation of Naturally Infected Canine Rabies Cases from Sri Lanka." BMC Veterinary Research 13 (April 12, 2017). https://doi.org/10.1186/s12917-017-1024-5.
"CDC - The Rabies Virus - Rabies." Accessed August 7, 2018. https://www.cdc.gov/rabies/transmission/virus.html.
Fisher, Christine R., Daniel G. Streicker, and Matthias J. Schnell. "The Spread and Evolution of Rabies Virus: Conquering New Frontiers." Nature Reviews Microbiology 16, no. 4 (February 26, 2018): 241–55. https://doi.org/10.1038/nrmicro.2018.11.
Hankins, Daniel G., and Julia A. Rosekrans. "Overview, Prevention, and Treatment of Rabies." Mayo Clinic Proceedings 79, no. 5 (May 1, 2004): 671–76. https://doi.org/10.4065/79.5.671.
"Rabies." World Health Organization. Accessed August 8, 2018. http://www.who.int/news-room/fact-sheets/detail/rabies.
Rupprecht, Charles E. "Rhabdoviruses: Rabies Virus." In Medical Microbiology, edited by Samuel Baron, 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston, 1996. http://www.ncbi.nlm.nih.gov/books/NBK8618/.
"The Rabies Virus | CDC Rabies and Kids." Accessed August 7, 2018. https://www.cdc.gov/rabiesandkids/virus.html.
University, © Stanford, Stanford, and California 94305 Copyright Complaints. "Rabies Virus Fact Sheet – Stanford Environmental Health & Safety." Accessed August 8, 2018. https://ehs.stanford.edu/reference/rabies-virus-fact-sheet.
- Rabies Images:
"CDC - Diagnosis: Histologic Examination - Rabies." Accessed August 7, 2018. https://www.cdc.gov/rabies/diagnosis/histologic.html.
Filovirus references:
Ansari, Aftab A. "Clinical Features and Pathobiology of Ebolavirus Infection." Journal of Autoimmunity 55 (December 2014): 1–9. https://doi.org/10.1016/j.jaut.2014.09.001.
Billioux, Bridgette Jeanne, Bryan Smith, and Avindra Nath. "Neurological Complications of Ebola Virus Infection." Neurotherapeutics 13, no. 3 (July 2016): 461–70. https://doi.org/10.1007/s13311-016-0457-z.
Feldmann, Heinz, and Hans-Dieter Klenk. "Filoviruses." In Medical Microbiology, edited by Samuel Baron, 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston, 1996. http://www.ncbi.nlm.nih.gov/books/NBK8129/.
Greslan, Thierry de, Magali Billhot, Claire Rousseau, Christine Mac Nab, Ludovic Karkowski, Jean-Marie Cournac, Julien Bordes, et al. "Ebola Virus–Related Encephalitis." Clinical Infectious Diseases 63, no. 8 (October 15, 2016): 1076–78. https://doi.org/10.1093/cid/ciw469.
"Infection Control for Viral Haemorrhagic Fevers in the African Health Care Setting | Viral Hemorrhagic Fevers (VHFs) | CDC." Accessed August 9, 2018. https://www.cdc.gov/vhf/abroad/vhf-manual.html.
McElroy, Anita K., Rama S. Akondy, Carl W. Davis, Ali H. Ellebedy, Aneesh K. Mehta, Colleen S. Kraft, G. Marshall Lyon, et al. "Human Ebola Virus Infection Results in Substantial Immune Activation." Proceedings of the National Academy of Sciences 112, no. 15 (April 14, 2015): 4719–24. https://doi.org/10.1073/pnas.1502619112.
McElroy, Anita K, Elke Mühlberger, and César Muñoz-Fontela. "Immune Barriers of Ebola Virus Infection." Current Opinion in Virology, Emerging viruses: intraspecies transmission • Viral Immunology, 28 (February 1, 2018): 152–60. https://doi.org/10.1016/j.coviro.2018.01.010.
Messaoudi, Ilhem, Gaya K. Amarasinghe, and Christopher F. Basler. "Filovirus Pathogenesis and Immune Evasion: Insights from Ebola Virus and Marburg Virus." Nature Reviews. Microbiology 13, no. 11 (November 2015): 663–76. https://doi.org/10.1038/nrmicro3524.
"Post-Exposure Therapy of Filovirus Infections- ClinicalKey." Accessed August 9, 2018. https://www-clinicalkey-com.proxy.medlib.uits.iu.edu/#!/content/playContent/1-s2.0-S0966842X14000730?returnurl=null&referrer=null.
Rhein, Bethany A., Linda S. Powers, Kai Rogers, Manu Anantpadma, Brajesh K. Singh, Yasuteru Sakurai, Thomas Bair, et al. "Interferon-γ Inhibits Ebola Virus Infection." PLOS Pathogens 11, no. 11 (November 12, 2015): e1005263. https://doi.org/10.1371/journal.ppat.1005263.
Stonier, Spencer W., Andrew S. Herbert, Ana I. Kuehne, Ariel Sobarzo, Polina Habibulin, Chen V. Abramovitch Dahan,
Rebekah M. James, et al. "Marburg Virus Survivor Immune Responses Are Th1 Skewed with Limited Neutralizing Antibody Responses." Journal of Experimental Medicine 214, no. 9 (September 4, 2017): 2563–72. https://doi.org/10.1084/jem.20170161.
Wong, Gary, Xiangguo Qiu, Gene G. Olinger, and Gary P. Kobinger. "Post-Exposure Therapy of Filovirus Infections." Trends in Microbiology 22, no. 8 (August 2014): 456–63. https://doi.org/10.1016/j.tim.2014.04.002.
- Filovirus Images:
Goldsmith, CDC/Cynthia. Ebola Virus Virion. Created by GC Microbiologist Cynthia Goldsmith, This Colorized Transmission Electron Micrograph (TEM) Revealed Some of the Ultrastructural Morphology Displayed by an Ebola Virus Virion. Public Health Image Library, #10816 https://commons.wikimedia.org/wiki/File:Ebola_virus_virion.jpg.