Download Bunyaviridae by Clayton M. Johnston

Bunyaviridae
Clayton M. Johnston
Bunyaviridae
• Largest family of mammal affecting viruses
(250 viruses)
• Arthropod- or rodent-borne vectors
• Most are amplified in vertebrate hosts
Bunyaviridae
Genus
Disease(s)
Bunyavirus LaCrosse encephalitis
Phlebovirus Rift Valley Fever
Nairovirus
Tospovirus
Crimean-Congo Hemorrhagic Fever
Plant Virus
Hantavirus
Hemorrhagic Fever with Renal
Syndrome
Hantavirus Pulmonary Syndrome
Structure
• Virion Structure
• Genomic Structure
• Structural Proteins
Virion Structure
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•
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Spherical
80-120 nm diameter
Enveloped
Helical nucleocapsid
NO matrix protein
Genomic Structure
• (-) sense
• Linear ssRNA
• Three segments:
– Large (L) codes for viral polymerase
– Medium (M) codes for G1 and G2
glycoproteins
– Small (S) codes for nucleocapsid
Structural Proteins
• Membrane Glycoproteins
• Nucleocapsid Protein
• Viral Polymerase
Structural Proteins
Membrane
glycoproteins
(G1 and G2)
Nucleocapsid
proteins (N)
Polymerase
(L)
Membrane Glycoproteins
• G1 and G2
• Integral membrane proteins
• Important in cell entry and pathogenesis
Nucleocapsid Protein
• Complexes with genomic vRNA in virus, as
well as with cRNA after infection, but not
with mRNA
• Necessary for virus replication and
packaging
Viral Polymerase
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•
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•
RNA-dependent RNA polymerase
Complexed with ribonucleocapsid in virion
Endonuclease activity to cleave host mRNA
Transcriptase activity for making cRNA and
mRNA from vRNA
• Helicase activity to unwind vRNA during
transcription
Viral Replication
• Receptor mediated endocytosis
• Occurs in cytoplasm
• Budding at Golgi apparatus or cell
membrane
Hantavirus Replication Cycle
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Attachment
Entry and Uncoating
Primary Transcription
Translation
Genome Replication
Secondary Transcription
Virion Assembly
Virion Release
Attachment
• Viral G1 and G2 glycoproteins interact with
cell surface receptors
• Pathogenic hantavirus bind β3 integrins
• Non-pathogenic hantaviruses bind β1
receptors
Entry and Uncoating
• Virus particles bound to integrin receptors are
taken in by receptor mediated endocytosis
• Newly formed vesicles are acidified
• Acidic environment changes confirmation of G1
and G2 glycoproteins
• Viral and cell membranes fuse
• Genomic material and polymerase are released
into cytoplasm
Attachment and Entry
Primary Transcription
• Transcription of negative sense vRNA to
mRNA
• Viral polymerase transcribes nucleoproteincoated vRNA
• Capped oligonucleotides from cell’s own
mRNA are used to prime transcription
(similar to Influenza virus)
Translation
• L and S segments of mRNA are translated
on free ribosomes in cytoplasm
• M segment mRNA is translated on ERbound ribosomes
Translation
Genome Replication
• vRNA is used as a template by viral
polymerase to make cRNA
• cRNA is used as a template to make more
negative sense strands of vRNA
Secondary Transcription
• Extra vRNA synthesized during replication
is used as template to make mRNA
• Since more template is present after vRNA
is replicated, more mRNA can be
transcribed, and more viral proteins can be
made
• Persistent infection
Virion Assembly
• Membrane-bound G1 and G2 peptides are
transported to Golgi apparatus and
carbohydrates are attached by N-linked
glycosylation
• vRNA complexes with N nucleocapsid
protein, forms looped panhandle structure,
and complexes with polymerase
Virion Assembly
Virion Release
Two Mechanisms
• Nucleocapsid complexes
bud into the Golgi
membrane with G1 and
G2 embedded
• Virion particle is formed
inside Golgi apparatus
• Virions are transported to
cell membrane by vesicles
and released by exocytosis
• G1 and G2 embed into
cell membrane through
Golgi vesicles
• Virions bud from cell
membrane, not through
Golgi apparatus
Attachment
Entry
Uncoating
Release
Transcription
Replication
Assembly
Translation
LaCrosse Encephalatis
Bunyavirus
• Mostly infects children younger than 16
• Ades mosquitoes are the common vector
• Squirrels and chipmunks are the amplifying
host
• Most common bunyavirus infection in the
United States
LaCrosse Encephalatis
Bunyavirus
• Targets the brain
• Symptoms may include:
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–
–
–
Fever
Convulsions
Drowsiness
Focal neurological signs
Rift Valley Fever
Phlebovirus
• Most spread by sandfly or Ades species of
mosquitoes
• Causes abortion in livestock
• Highly infectious by aerosolized blood
• Distribution follows that of the host vectors
• Immunization of livestock is the most
effective way to control and prevent the
disease
Rift Valley Fever
Phlebovirus
• Febrile disease in humans
• Targets the liver
• Symptoms often include:
– Fever
– Encephalitis
– Retinal vasculitis (which may lead to blindness)
Rift Valley Fever
Distribution Map
Crimean-Congo Hemorrhagic Fever
Nairovirus
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Transmitted by ticks
Appears in the Middle East and Africa
Targets the liver and vascular endothelium
Symptoms include:
– Headache
– Pain in limbs
– Often bleeding from many orifices
Crimean-Congo Hemorrhagic Fever
Nairovirus
Hantavirus
• Enveloped
• ssRNA
• Virions 98 nm in
diameter
• Genome consists of
three RNA segments
Transmission
Vectors
• Transmitted via aerosolized rodent urine,
feces, and saliva
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Deer mouse (Peromyscus maniculatus)
Cotton rat (Sigmodon hispidus)
White-footed mouse (Peromyscus leucopus)
Striped field mours (Apodemus agrarius)
Bank vole (Clethrionomys glareolus)
Rat (Rattus)
Hemorrhagic Fever with Renal Syndrome
Hantavirus
• Liver and vascular enothelium are targeted
• Symptoms include:
– Hemorrhage
– Acute renal failure
– Fever
• Over 15% mortality rate
Hantavirus Pulmonary Syndrome
Hantavirus
• Lungs are targeted
• Symptoms include
– Fever
– Acute respiratory distress
• Over 50% mortality rate
• Shock and cardiac complications often
contribute to death
Prevention and Control
• Vaccines
• Hygiene
• Vector Control
Vaccines
• E. coli expressed truncated nucleocapsid as
an immunogen
• Naked DNA
• Recombinant non-pathogenic virus
• Rodent brain-derived
• Cell culture derived
• Inactivated virus – being tried out in China
Hygiene
• Prevent aerosolization of virus from roden
excrement
• Dampen surfaces with bleach before
cleaning
• Control rodents and human contact with
rodents
Host Defenses and Immune Response
• Interferon is produced
• Humor antibody has been shown to be
related to the disappearance of virus from
blood
• Cytotoxic T-cells attack infected host cells
• Inflammatory response
Treatment
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Early aggressive intensive care
Early use of inotropic agents (Dobutamine)
Early ventilation
Careful monitoring:
– Oxygenation
– Fluid balance
– Blood pressure
Treatment
• General care, alleviation of symptoms
• Ribavirin (Hemorrhagic Fever with Renal
Syndrome)
• ECMO (Hantavirus Pulmonary Syndrome)
Ribavirin
• Administered
intravenously
• Shown to be effective
against Hemorrhagic
Fever with Renal
Syndrome
• Not shown to be effective
against Hantavirus
Pulmonary Syndrome
causing strains
Extra Corporeal Membrane Oxygenation
(ECMO)
• Removes blood from the body and
artificially removes CO2 and adds O2
• Costly
• Difficult
ECMO
Laboratory Diagnosis
• Serology (ELISE for IgM)
• Immunohistochemistry
• Reverse transcription and polymerase chain
reaction (RT-PCR)
• Virus isolation
• Direct detection of antigen in blood and
urine
• Immunofluorescent test for antibodies
Problems Diagnosing Hantavirus
• Symptoms often confused with influenza
• Common signs of upper respiratory disease
such as sore throat, sinusitis, and ear pain
not usually present
• Abdominal pain often misinterpreted as
appendicitis
• Many doctors outside endemic regions fail
to recognize or have sufficient testing
Friday, March 26, 2004
PARKS AND PEOPLE
Glacier National Park
Death of Jerry O'Neal
The employees of Glacier National Park are deeply saddened to learn of
the untimely passing of Deputy Superintendent Jerry O'Neal. O’Neal
died early yesterday morning at a Kalispell, Mont., hospital following
a brief illness.
O'Neal, 61, came down with an unknown illness last week and had
undergone blood work and other diagnostic tests over the past few
days. He was admitted to the Kalispell Regional Medical Center on
Wednesday and died at 5:30 a.m. Thursday.
Friday, April 2, 2004
OPERATIONS NOTE
Public Health
Hantavirus Update
In view of the untimely death of Glacier National Park Deputy Superintendent Jerry
O'Neal on March 25th from hantavirus pulmonary syndrome, we are issuing the
following precautions and annual reminders.
Hantavirus pulmonary syndrome (HPS) is a viral disease transmitted to humans
primarily through the inhalation of airborne dusts laden with the virus from
infected rodent droppings (urine and saliva may also be sources of infection).
Although hantaviruses have been a threat to human health worldwide for at least 50
years, HPS was first recognized in the United States in 1993 around the Four
Corners area of the Southwest. Since then it has since been identified throughout
the United States. Although rare, HPS is potentially deadly – mortality rates
between 40 and 50% are common.