1. Paramyxoviruses; Rubella
Chapter 40

2. 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)

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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)

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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 nt
NiP - 27 nt
Six genes
N - nucleocapsid
P - phosphoproteins
M - matrix protein
F - fusion protein
G - glycoprotein (mediates attachment)
L - Large polymerase

15. Henipaviruses

16. Henipaviruses

17. 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

18. Henipaviruses

19. Henipaviruses Infections Bats - no apparent pathology
Horses (HeV) and pigs (NiV)
Respiratory transmission (communicable)
Neurological manifestations
Facial swelling
Nasal discharge
Humans
Severe acute encephalitis
NiV manifestations can occur up to 4 years post infection
Relapse encephalitis

20. Henipaviruses Molecular biology of infection G protein F 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