Flashcards in Thirty Five Deck (17):
What is the structure of RSV? Dissemination/infection in body? Which individuals become infected?
Pneumoviruses: respiratory syncytial virus (RSV)
- Lack an N protein (like measles)
- Infection of human respiratory epithelial
cells causes formation of syncytia and cell
death- airways become clogged with
mucus and debris
- No associated viremia
- Associated with outbreaks in healthy
children in daycare and hospitals (highly
- Opportunistic pathogen of elderly and
How does transmission occur? What are the symptoms in children? What are the symptoms in adults? When does this disease occur?
- Transmission via respiratory secretions
- Virus can be infectious on inanimate
objects for hours, including on hands
- Children get bronchitis, croup,
bronchiolitis, pneumonia. Children with
heart or lung disease at high risk of
- Adults get a “common cold” or bronchitis.
- Infection is unfortunately quite common
and these disease causes outbreaks every winter
Why is RSV so serious? What treatment is there? Prevention?
– Causes 40% of childhood pneumonias (thousands of
– Most common cause of pneumonia in children<1 year
– Healthy children can become extremely ill and cough for weeks afterward (parents cant sleep)
– Immunity is short-lived. Reinfection occurs even in
healthy children with the same antigenic form
– Supportive care only, no vaccines available.
Palivizumab (monoclonal antibody to RSV) used in high
risk children (premies and children with chronic lung
disease) during RSV season. Not completely effective
but reduces risk of severe disease. Unhelpful once
– Disease is seasonal (Nov to April)
– Patients are isolated to prevent spread in hospitals
– No vaccine available
What does severe RSV lead to? How is it treated?
Severe RSV leads to airway
-noisy breathing (stridor)
due to clogging of airway
May need emergency
How is obstructive bronchiolitis caused by RSV? What does it result in?
Dead cells, mucus, and fibrin clog small airways
• Cough and fever
• Copious nasal discharge and congestion, nasal flaring
• Expiratory wheezing, air trapping, rapid breathing
• Retraction of subcostal spaces
What is the structure of orthomyxoviruses? Where do they replicate in the cell?
• - strand segmented RNA genome (8 segments),
• Infects multiple mammalian and avian species
• Hemagglutinin mediates cell
attachment. H and N proteins
are expressed separately. No F
• Neuraminidase mediate virus
release from host cells
• Only RNA virus (other than
retroviruses) which replicates in
Describe the transmission of influenza.
• Dispersion of small-particle aerosols created by
sneezing, coughing, and talking (respiratory
• Extremely infectious. A single infected person can
transmit virus to a large number of susceptible
individuals in crowded places (airplanes, buses)
• Viral survival in aerosols appears to be favored by low
humidity and temperature- better flu transmission in
• Virus can survive on surfaces and
be re-aerosolized as an infectious
particle or be acquired from surface
Describe the pathogenesis and dissemination of influenza.
• Virus attaches to and penetrates columnar
• After adsorption, virus replication begins,
leading to cell death through several
– Dramatic shutoff of host-cell protein synthesis that occurs at several levels
– Also causes cell death by apoptosis
• Virus release continues for several hours
before cell death ensues
• Time between the incubation period and the
onset of illness and virus shedding 18-72 hrs
• Does not disseminate into blood but can
cause systemic disease
Describe the life cycle of influenza and how that applies to treatment.
Hemagglutinin mediates attachment
Receptor: Sialic acid residues
Hemagglutinin from vaccination or prior infection blocks viral attachment
Uncoating (blocked by amantadine)
RNA enters nucleus, replicates
Neuraminidase: facilitates virion release
Zanamivir/oseltamivir block neuraminidase
Describe the viral replication of orthomyxoviruses (virulence factors)
-virions contain P protein which snatches cap from host cell mRNA
-these caps protect viral RNA from degradation and
increase viral protein synthesis by facilitating translation
-Daughter virions assemble at host cell membrane; viral
neuraminidase prevents binding to host cell sialic acid
residues and facilitates infection of neighboring cells
What is the clinical course of influenza?
• Sudden onset of symptoms after an
incubation period of 1 to 2 days
• Many people can identify the hour of onset
• Fever, headache, myalgias, fatigue, non-
• Symptoms persist for the duration of the
fever, usually 3-5 days. Cough and
fatigue may last longer
What are some influenza complications? What is the leading cause of death?
• Primary Influenza Pneumonia-rare
• Flu kills ciliated columnar epithelial
cells- leaves patient vulnerable to
secondary Bacterial Pneumonia-
Staphylococcus aureus, Streptococcus
pneumoniae, Hemophilus influenzae
(leading cause of death from flu)
• Bronchiolitis and bronchitis, COPD
• Rare: encephalitis, meningitis, myositis,
Compare and contrast Influenza A and B. Compare and contrast the treatment of them.
• Influenza A: responsible for most
disease. Undergoes antigenic shift and
• Influenza A can be treated with
• Influenza B: responsible for local
outbreaks, often late in flu season.
Undergoes antigenic drift.
• Influenza B: amantidine/rimantidine not
effective. Neurominidase inhibitors are.
What are the properties of influenza that allow it to undergo mutagenesis. Describe antigenic drift and antigenic shift.
• Influenza A can jump species easily (humans, pigs,birds)
• Viral RNA polymerase is low fidelity, thus mutations are inserted with each replication cycle.
• Segmented genome allows for genetic reassortment if 2 daughter viruses infect same cell.
• Antigenic Drift: single amino acid mutations (mostly in H, occ. N)- happens constantly due to low fidelity polymerase- this is why flu is different every year (and we need a new flu vaccine every year).
• Evades pre-existing immunity by changing amino acids in antigenic portions of surface glycoproteins. Our antibodies are not as effective at recognizing the new configuration
Antigenic Shift: Genome allows reassortment of gene segments when multiple viruses infect a single cell
viruses can derive from different species resulting in introduction of new virus into naïve species (bird to human, often through reassortment in swine)
• Produces new strain of flu: H5N1, H1N1
• Results in new combination of surface proteins; pre-existing antibodies cannot recognize new virus to which entire human population is naive.
How is influenza diagnosed?
• Viral Cultures
– 90% detected in 3 days
– Rest in 5-7 days
• Rapid Detection in Respiratory Secretions
– Higher sensitivity in early course of disease
– 85-100% specificity
– Results in minutes
– Less sensitive than cell culture
How is the flu treated?
• We have drugs that interfere with functions of 2 viral
- amantidine and rimantidine block viral uncoating in
host cells by influenza A viruses
- oseltamivir* and zanamivir block release of infectious virions from host cells by influenza A and B
BOTH induce rapid viral resistance on therapy (only 1
viral base pair needs to mutate)
BOTH are effective only if given within 2 days of onset
BOTH can prevent infections if given quickly in outbreak