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Filoviruses, including Ebolavirus and Marburgvirus, are filamentous RNA viruses responsible for severe hemorrhagic fevers with high fatality rates, reaching up to 90%. Initially identified in outbreaks in the late 1960s and mid-1970s in Africa, these viruses spread through close contact with infected individuals. While there is no known treatment, experimental vaccines have shown promise. Bats are suspected reservoirs of these viruses, and they remain a significant public health concern, with sporadic outbreaks still occurring in various regions.
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Filoviruses • Chapter 38
Filoviruses • Filamentous RNA viruses • Africa, Philippines • Two genera • Ebolavirus • Marburgvirus (Africa only) • Cause hemorrhagic fevers with high fatality rates (up to 90%) • Infection appears to be by close contact with infected person • Highly contagious • First outbreak: 1967 (Marburg, Germany; Yugoslavia) • Vaccine company was processing primary kidney cells from African green monkeys (Cercopithecus aethiops) • Several workers developed a hemorrhagic fever • Several dozen infected by person-to-person transmission • Fewer than half died
Filoviruses • First Ebola outbreak: 1976 (Zaire, Sudan) • Hundreds infected • 70%-90% fatal • Sporadic outbreaks still occur in Africa • Three viruses • Ebola Zaire • Ebola Sudan • Ebola Reston (Virginia) • Reston, Virginia outbreak • Occurred in a monkey quarantine facility (JRH Biosciences) • Monkeys imported from Philippines began dying from HF • Samples sent to nearby military lab for ID • United States Army Medical Research Institute for infectious Diseases (USAMRIID) • EM showed shepherd’s crook particles • Facility was secured by Army • Nonpathogenic in humans
Filoviruses • Ecology • Suspected bat reservoirs • Unknown vector (if any) • Clinical spectrum • Vascular leakage • Viremia (high titer) • Bleeding from orifices • Disseminated intravascular coagulation • No known treatment • Vaccine • Experimental • Developed in 2005 • Protects guinea pigs from infection • Bioweapon • Soviets weaponized Marburg virus • Japanese cult Aum Shrinrkyo attempted to obtain an Ebolavirus
Bats are reservoirs? • Suspected Ebola virus hosts • Epomops franqueti (Franquet's epauleted bat) • Hypsignathus monstrosus (hammer-headed bat) • Myonycteris torquata (little collared fruit bat) • Suspectecte Marburg virus host • Rousettus aegyptiacus (Egyptian fruit bat)
Case History Ebola Reston excluded
Case History Ebola Reston excluded
Case History Ebola Reston excluded
Filoviruses • Negative-strand virus • 7 to 9 mRNAs • NP - nucleoprotein • polymerizes with vRNA into a spiral tube • VP35 - nonstructural • Type 1 interferon antagonist • Inhibits interferon response elements found in the promoters of many antiviral genes • Suppresses the pathway regulated by dsRNA-dependent protein kinase PKR • VP40 - matrix protein • GP - glycoprotein spike • lectin-specific • GP1 binding • GP2 fusion • VP30 - transcription factor • VP24 - virus assembly, STAT1 inhibitor • L - RNA-dependent RNA polymerase
Pathogenesis • Major clinical feature is inflammatory response resembling septic shock • Nonhuman primate models show initial replication in • Monocytes • Macrophages • Dendritic cells (blocking maturation to APC) • Some of these cells disseminate virus throughout the body • A systemic cytokine and chemokine inflammatory response occurs • Multisystem organ failure • Cell surface tissue factor triggers extrinsic coagulation pathway • Disseminated intravascular coagulation occurs • Endothelial cell infection appears late in disease • Two viral proteins suppress the type I interferon response • VP35 protein inhibits activation of interferon regulatory factor 3 • VP24 blocks STAT1 localization to the nucleus • Lymphocytes die by apoptosis (and not viral infection)
