Transcript 14 Paramyxoviruses

Paramyxoviruses;
Rubella
Chapter 40
Paramyxoviruses
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Features
ssRNA viruses
Nonsegmented, ~15 kb
Enveloped
Hemagglutinin glycoprotein
Fusion glycoprotein
Labile, but highly infections
Major classification (Paramyxovirinae)
Respirovirus (parainfluenza viruses)
Rubulavirus (mumps, parainfluenza viruses)
Morbillivirus (measles)
Henipavirus (Hendra and Nipah viruses)
Pnuemovirus (respiratory syncytial virus)
Metapneumovirus (metapneumovirus)
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Measles
Symptoms
Begins with fever, runny nose, cough, red
weepy eyes
Fine rash appears within a few days
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Symptoms generally disappear within 1 week
Many cases complicated by secondary
infections
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Appears first on forehead, then spreads to rest of body
Pneumonia and earaches are most common
secondary conditions
Less common complications include encephalitis and
subacute sclerosing panencephalitis (SSPE)
Measles does not kill; instead, it leads to
secondary infections that do kill
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Measles
Pathogenesis
Infection via respiratory route
Virus replicates in epithelium of upper respiratory
tract
Spreads to lymph nodes
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Further replication occurs here
Spreads to all parts of the body
Infected mucous membranes important diagnostic
sign
Membranes covered with Koplik spots
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White spots seen in back of throat opposite molars
Infected membranes may explain increased
susceptability to secondary infection
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Especially to middle ear and lungs
Skin rash is due to effects of virus replication
within skin cells
Rash also due to cellular immune response to
viral antigens in the skin
Measles
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Epidemiology
Humans are only natural host
Virus spread by respiratory droplets
Before routine immunization, over 99% of population infected
Vaccine resulted in decline of annual cases
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• Measles is no longer endemic in United States
• Outbreaks still occur and are due to susceptible populations
• Populations include
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Children too young to be vaccinated
Preschool children never vaccinated
Children and adults inadequately vaccinated
Persons not vaccinated for religious or medical reasons
Prevention and Treatment
Prevention by vaccination
Vaccine is usually given in conjunction with mumps and rubella
vaccine
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MMR
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Measles
Measles virulence factors
• P protein
• Transcription factor for cellular enzyme
A20
• A20 negatively regulates NF-κB
• NF-κB activates antiviral responses in
infected cells
• V protein
• Blocks JAK phosphorylation of STAT1
• Blocks STAT1/STAT2 dimerization
• C protein interferes with PKR
Measles as a Global Health Problem
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Measles occurs predominantly in Africa and Asia
In 2000, there were more than 700,000 deaths per year from
measles
The great majority of these deaths were children
In 2001 the Measles Initiative was started by the WHO
Deaths in 2005 were 454,000
Deaths in 2010 were 164,000
A 90% reduction is targeted by 2010 (from 2000 levels)
Vigorously supported by Rotary International
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Rubella
• Aka - German Measles
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Typically mild
Often unrecognized
Difficult to diagnose
Significant infection in pregnant women
Symptoms
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Slight fever with mild cold symptoms
Enlarged lymph nodes behind ears and back of neck
Faint rash on face
Rash consists of light pink spots
Adults commonly complain of joint pain
Symptoms last only a few days
Joint pain may last up to 3 weeks
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Congenital rubella syndrome
First trimester susceptibility highest
Can lead to fetal death, or neurological disease in survivors
(deafness, mental retardation)
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Rubella
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Causative Agent
Rubella virus
Member of Togaviridae family
Small, enveloped
Single-stranded RNA genome
Pathogenesis
Enters body via respiratory route
Virus multiplies in nasopharynx, then enters bloodstream
Causes sustained viremia
Blood transports virus to body tissues
Immunity develops against viral antigens resulting antigenantibody complexes most likely responsible for rash and joint
pain
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Rubella
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Epidemiology
Humans are only natural host
Disease is highly contagious
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Less so than measles
40% of infected people fail to develop symptoms
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These individuals can spread virus
Infectious 7 days before appearance of rash to 7 days after
Prevention and Treatment
Vaccination with attenuated rubella virus vaccine
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Administered at 12 months and boosted at 4 to 6 years of age
Produces long-lasting immunity in 95% of recipients
Vaccine not given to pregnant women due to potential complications
Women are advised not to become pregnant for 28 days post
vaccination
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Vaccine has significantly reduced incidence in United States
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Mumps
Causative Agent
Mumps virus
Member of the Paramyxoviridae family
Enveloped
Single stranded RNA genome
Symptoms
Early symptoms
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Fever with loss of appetite and headache
Later symptoms
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Painful swelling of one or both parotid glands and spasms
Usually makes it difficult to chew and swallow
Symptoms disappear in about a week
Symptoms much more severe in individuals past puberty
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Post-pubertal males can suffer painful swelling of testicles
Ovarian involvement occurs in about 20% of cases
Pregnant women often miscarry
Mumps
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Pathogenesis
Transmitted by inhalation of infected droplets
Long incubation period
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15 to 20 days
Virus replicates in the upper respiratory tract
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Virus spreads throughout body via bloodstream
Produces symptoms after infecting tissues
In salivary glands
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Virus multiplies in epithelium of salivary ducts
Destroys epithelium and releases virus into saliva
Inflammation produced
Inflammation responsible for symptoms and pain
Mumps
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Epidemiology
Humans only natural host
Natural infection confers lifelong immunity
Virus is spread by asymptomatic individuals in high numbers
Virus can be present in saliva of symptomatic persons
Prevention and Treatment
Prevention directed at immunization
Usually given in same injection as measles and rubella
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MMR
Immunization prevents latent recurrent infections
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Due to only one viral serotype
No effective antiviral treatment
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Henipaviruses
Members
Hendra virus (HeV; Australia)
Nipah virus (NiV; Asia)
Paramyxoviruses
Subfamily Paramyxovirinae
Bat viruses
Genus Pteropus (flying foxes)
Genome organization
Negative strand RNA
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HeV - 18.2 nt
NiP - 27 nt
Six genes
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N - nucleocapsid
P - phosphoproteins
M - matrix protein
F - fusion protein
G - glycoprotein (mediates attachment)
L - Large polymerase
Henipaviruses
Henipaviruses
Henipaviruses
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Features
Only zoonotic paramyxoviruses
Infections
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Bats
Humans
Horses
Pigs
Dogs
Ferrets
Raccoons
Lions
Hamsters
2004 Bangladesh outbreak: 75% fatality rate
BSL-4 pathogens and select agents
Henipaviruses
Henipaviruses
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Infections
Bats - no apparent pathology
Horses (HeV) and pigs (NiV)
Respiratory transmission (communicable)
Neurological manifestations
Facial swelling
Nasal discharge
Humans
Respiratory transmission (communicable)
Severe acute encephalitis
NiV manifestations can occur up to 4 years post infection
Relapse encephalitis
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Henipaviruses
Molecular biology of infection
G protein
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Provides broad species tropism
Along with F protein can induce fusion of cells from different species
Cellular receptor is ephrin B2 protein
Neurons
Smooth muscle
Capillary endothelial cells
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F protein
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Single polypeptide (F0) is cleaved into F1 and F2 by cellular furin
protease in the Golgi
F1 and F2 are disulfide-linked on virus membrane to form F protein
P gene
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Single polypeptide cleaved into P, V and W proteins
P and V interact with and disable STAT1 transcription factor
W interacts with and disables IRF-3 transcription factor
These events disable the type I IFN pathway of infected cells