paramyxoviruses; rubella chapter 40. paramyxoviruses features ssrna viruses nonsegmented, ~15 kb...
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Paramyxoviruses; Rubella
Chapter 40
Paramyxoviruses
• 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)
Measles• Symptoms
• Begins with fever, runny nose, cough, red weepy eyes
• Fine rash appears within a few days• Appears first on forehead, then spreads to rest of
body
• Symptoms generally disappear within 1 week
• Many cases complicated by secondary infections• 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
Measles• Pathogenesis
• Infection via respiratory route
• Virus replicates in epithelium of upper respiratory tract
• Spreads to lymph nodes• Further replication occurs here
• Spreads to all parts of the body
• Infected mucous membranes important diagnostic sign
• Membranes covered with Koplik spots• White spots seen in back of throat opposite molars
• Infected membranes may explain increased susceptability to secondary infection• 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• 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• Measles is no longer endemic in United States
• Outbreaks still occur and are due to susceptible populations
• Populations include• 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• MMR
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
• 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
Rubella• Aka - German Measles
• Typically mild
• Often unrecognized
• Difficult to diagnose
• Significant infection in pregnant women
• Symptoms• 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
• Congenital rubella syndrome
• First trimester susceptibility highest
• Can lead to fetal death, or neurological disease in survivors (deafness, mental retardation)
Rubella
• 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 antigen-antibody complexes most likely responsible for rash and joint pain
Rubella
• Epidemiology
• Humans are only natural host
• Disease is highly contagious• Less so than measles
• 40% of infected people fail to develop symptoms• 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• 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
• Vaccine has significantly reduced incidence in United States
Mumps• Causative Agent
• Mumps virus
• Member of the Paramyxoviridae family
• Enveloped
• Single stranded RNA genome
• Symptoms
• Early symptoms• Fever with loss of appetite and headache
• Later symptoms• 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• Post-pubertal males can suffer painful swelling of testicles
• Ovarian involvement occurs in about 20% of cases
• Pregnant women often miscarry
Mumps
• Pathogenesis
• Transmitted by inhalation of infected droplets
• Long incubation period• 15 to 20 days
• Virus replicates in the upper respiratory tract• Virus spreads throughout body via bloodstream
• Produces symptoms after infecting tissues
• In salivary glands• Virus multiplies in epithelium of salivary ducts
• Destroys epithelium and releases virus into saliva
• Inflammation produced
• Inflammation responsible for symptoms and pain
Mumps
• 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• MMR
• Immunization prevents latent recurrent infections• Due to only one viral serotype
• No effective antiviral treatment
Henipaviruses• Members
• Hendra virus (HeV; Australia)
• Nipah virus (NiV; Asia)
• Paramyxoviruses
• Subfamily Paramyxovirinae
• Bat viruses
• Genus Pteropus (flying foxes)
• Genome organization
• Negative strand RNA• HeV - 18.2 nt
• NiP - 27 nt
• Six genes• N - nucleocapsid
• P - phosphoproteins
• M - matrix protein
• F - fusion protein
• G - glycoprotein (mediates attachment)
• L - Large polymerase
Henipaviruses
Henipaviruses
Henipaviruses
• Features
• Only zoonotic paramyxoviruses
• Infections• Bats
• Humans
• Horses
• Pigs
• Dogs
• Ferrets
• Raccoons
• Lions
• Hamsters
• 2004 Bangladesh outbreak: 75% fatality rate
• BSL-4 pathogens and select agents
Henipaviruses
Henipaviruses
• 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
Henipaviruses• Molecular biology of infection
• G protein• 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
• F protein• 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• 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
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