Paramyxoviruses; Rubella

Chapter 40

Paramyxoviruses

• • • • • • Features ssRNA viruses Nonsegmented , ~15 kb • • Enveloped Hemagglutinin Fusion glycoprotein glycoprotein Labile, but highly infections • • • • • • Major classification (

Paramyxovirinae

)

Respirovirus

(parainfluenza viruses)

Rubulavirus Morbillivirus Henipavirus Pnuemovirus

(mumps, parainfluenza viruses) (measles) (Hendra and Nipah viruses) (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 secondary conditions are most common 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 tract • Spreads to lymph nodes Further replication occurs here Spreads to all parts of the body upper respiratory 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

• • • • • • • Aka - German Measles

Rubella

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

Small, enveloped family 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

Enveloped Single stranded RNA genome family • • • • 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 Nipah virus (HeV; Australia) (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 protein • • • Cellular receptor is ephrin B2 Neurons Smooth muscle Capillary endothelial cells • F protein Single polypeptide (F 0 ) is cleaved into F 1 and F 2 by cellular furin protease in the Golgi • F 1 and F 2 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