Filoviruses Chapter 38. Filoviruses Filamentous RNA viruses Africa, Philippines Two genera...
-
Upload
ferdinand-bishop -
Category
Documents
-
view
222 -
download
0
Transcript of Filoviruses Chapter 38. Filoviruses Filamentous RNA viruses Africa, Philippines Two genera...
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 HistoryVirus and date of onset
Epicenter(s)Source of primary
infectionFactors contributing to spread
#Cases
CFR (%)
Marburgvirus
1967Marburg and
Frankfurt, Germany;Imported monkeys
from UgandaDissection of monkeys to harvest organs,
nosocomial transmission32 22
1975Rhodesia (present Zimbabwe)/South
AfricaUnknown Nosocomial transmission 3 33
1980Kisumu and Nairobi,
KenyaExposure in cave? Monkey contact?
Nosocomial transmission 2 50
1987 Mombasa, Kenya Exposure in cave? – 1 100
1998 Durba, DRCExposure in gold
mineRepeated primary introductions into
humans154 83
2004 Uíge, Angola UnknownNosocomial and community-based
transmission252 90
2007 Kamwenge, UgandaExposure in gold
mine?
Presumed primary introductions in 2 cases, with subsequent person–person
spread4 25
Ebola Reston excluded
Virus and date of onset
Epicenter(s)Source of primary
infectionFactors contributing to spread
#Cases
CFR (%)
Zaire ebolavirus
1976Yambuku, Zaire (present DRC)
Unknown Nosocomial transmission 318 88
1977 Tandala, Zaire Unknown – 1 100
1994Ogooué-Ivindo
Province, GabonUnknown
Traditional healing practices, nosocomial and community-based transmission
49 59
1995 Kikwit, DRC Unknown Nosocomial transmission 315 81
1996Ogooué-Ivindo
Province, GabonConsumption of dead
chimpSecondary spread to caregivers 31 68
1996Ogooué-Ivindo
Province, GabonUnknown
Exposure while hunting, traditional healing practices
60 75
1996Johannesburg, South Africa
Imported from Gabon by infected doctor
Nosocomial transmission 2 50
2001Ogooué-Ivindo
Province, Gabon
Hunting and consumption of
nonhuman primates
Exposure while hunting, secondary spread to caregivers, traditional healing
practices124 78
2002Cuvette Ouest Region, ROC
Hunting and consumption of
nonhuman primates
Exposure while hunting, secondary spread to caregivers
143 89
2003Cuvette Ouest Region, ROC
Hunting and consumption of
nonhuman primates
Exposure while hunting, secondary spread to caregivers
35 83
2007Kasai Occidental Province, DRC
Unknown Unknown 264 71
Case History
Ebola Reston excluded
Virus and date of onset
Epicenter(s)Source of primary
infectionFactors contributing to spread
#Cases
CFR (%)
Sudan ebolavirus
1976Maridi and Nzara,
SudanUnknown Nosocomial transmission 284 53
1979 Nzara, Sudan Unknown Nosocomial transmission 34 65
2000 Gulu, Uganda Unknown Nosocomial and community transmission 425 53
2004 Yambio, Sudan Unknown Unknown 17 41
Ivory Coast ebolavirus
1994Taï Forest, Côte
d’IvoireNecropsy of chimpanzee
– 1 0
Ebolavirus, un-known species
2007Bundibugyo District,
UgandaUnknown Unknown 149 25
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)