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

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 shepherds 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
Virus and
date of
onset

Epicenter(s)

Source of primary
infection

Factors contributing to spread

#Cas CFR
es
(%)

Marburgviru
s
1967

Marburg and
Frankfurt, Germany;

Imported monkeys Dissection of monkeys to harvest organs,

from Uganda
nosocomial transmission

1975

Rhodesia (present
Zimbabwe)/South
Africa

Unknown

1980

Kisumu and Nairobi,

Kenya

1987

32

22

Nosocomial transmission

33

Exposure in cave?
Monkey contact?

Nosocomial transmission

50

Mombasa, Kenya

Exposure in cave?

100

1998

Durba, DRC

Exposure in gold
mine

Repeated primary introductions into

humans

154

83

2004

Uge, Angola

Unknown

Nosocomial and community-based

transmission

252

90

Kamwenge, Uganda

Exposure in gold
mine?

Presumed primary introductions in 2

cases, with subsequent personperson
spread

25

2007

Ebola Reston excluded

Case History
Virus and
date of
onset

Epicenter(s)

Source of primary
infection

Factors contributing to spread

#Cas CFR
es
(%)

1976

Yambuku, Zaire
(present DRC)

Unknown

Nosocomial transmission

318

88

1977

Tandala, Zaire

Unknown

100

1994

Ogoou-Ivindo
Province, Gabon

Unknown

Traditional healing practices, nosocomial

and community-based transmission

49

59

1995

Kikwit, DRC

Unknown

Nosocomial transmission

315

81

1996

Ogoou-Ivindo
Province, Gabon

Consumption of dead
chimp

Secondary spread to caregivers

31

68

1996

Ogoou-Ivindo
Province, Gabon

Unknown

Exposure while hunting, traditional

healing practices

60

75

1996

Johannesburg,
South Africa

Imported from Gabon

by infected doctor

Nosocomial transmission

50

2001

Ogoou-Ivindo
Province, Gabon

Hunting and
consumption of
nonhuman primates

Exposure while hunting, secondary

spread to caregivers, traditional healing
practices

124

78

2002

Cuvette Ouest
Region, ROC

Hunting and
consumption of
nonhuman primates

Exposure while hunting, secondary

spread to caregivers

143

89

2003

Cuvette Ouest
Region, ROC

Hunting and
consumption of
nonhuman primates

Exposure while hunting, secondary

spread to caregivers

35

83

2007

Kasai Occidental
Province, DRC

264

71

Zaire
ebolavirus

Unknown
Ebola Reston excluded

Unknown

Case History
Virus and
date of
onset

Epicenter(s)

Source of primary
infection

Factors contributing to spread

#Cas CFR
es
(%)

1976

Maridi and Nzara,

Sudan

Unknown

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

Ta Forest, Cte
dIvoire

Necropsy of
chimpanzee

Bundibugyo District,
Uganda

Unknown

Unknown

149

25

Sudan
ebolavirus

Ivory Coast
ebolavirus
1994
Ebolavirus,
un-known
species
2007

Ebola Reston excluded

Filoviruses

Filoviruses

Filoviruses

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

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)

Jak/STAT
Pathway