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Flashcards in Thirty Five Deck (17):
1

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

infectious virus)

- Opportunistic pathogen of elderly and

immunocompromised

2

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

pneumonia

- Adults get a “common cold” or bronchitis.

- Infection is unfortunately quite common
and these disease causes outbreaks every winter

3

Why is RSV so serious? What treatment is there? Prevention?

– Causes 40% of childhood pneumonias (thousands of

hospitalizations annually)

– 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

infection started

– Disease is seasonal (Nov to April)

– Patients are isolated to prevent spread in hospitals

– No vaccine available

4

What does severe RSV lead to? How is it treated?

Severe RSV leads to airway

obstruction (laryngotracheobronchitis)

-noisy breathing (stridor)

due to clogging of airway

with secretions

-Hoarse voice

-Wheezing

May need emergency

therapy with

epinephrine/inhaled

steroids

5

How is obstructive bronchiolitis caused by RSV? What does it result in?

Dead cells, mucus, and fibrin clog small airways

Disease manifestations:

• Cough and fever

• Copious nasal discharge and congestion, nasal flaring

• Expiratory wheezing, air trapping, rapid breathing

• Retraction of subcostal spaces

6

What is the structure of orthomyxoviruses? Where do they replicate in the cell?

• - strand segmented RNA genome (8 segments),
enveloped virus

• Infects multiple mammalian and avian species

• Hemagglutinin mediates cell

attachment. H and N proteins

are expressed separately. No F

protein.

• Neuraminidase mediate virus

release from host cells

• Only RNA virus (other than

retroviruses) which replicates in

the nucleus

7

Describe the transmission of influenza.

• Dispersion of small-particle aerosols created by

sneezing, coughing, and talking (respiratory

secretions)

• 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

winter time.

• Virus can survive on surfaces and

be re-aerosolized as an infectious

particle or be acquired from surface

8

Describe the pathogenesis and dissemination of influenza.

• Virus attaches to and penetrates columnar

epithelial cells

• After adsorption, virus replication begins,

leading to cell death through several

mechanisms

– 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

9

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

Endocytosis,

Uncoating (blocked by amantadine)

RNA enters nucleus, replicates

Translation/Processing/Assemblyl

Neuraminidase: facilitates virion release
Zanamivir/oseltamivir block neuraminidase

10

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

11

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-
productive cough

• Symptoms persist for the duration of the

fever, usually 3-5 days. Cough and

fatigue may last longer

12

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

exacerbation, asthma

• Rare: encephalitis, meningitis, myositis,

myocarditis

13

Compare and contrast Influenza A and B. Compare and contrast the treatment of them.

• Influenza A: responsible for most

disease. Undergoes antigenic shift and

drift

• Influenza A can be treated with

amantidine/rimantidine and

neurominidase inhibitors

• Influenza B: responsible for local

outbreaks, often late in flu season.

Undergoes antigenic drift.

• Influenza B: amantidine/rimantidine not

effective. Neurominidase inhibitors are.

14

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.

15

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

16

How is the flu treated?

• We have drugs that interfere with functions of 2 viral
proteins:

- 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
of symptoms

BOTH can prevent infections if given quickly in outbreak
situations

17

How can the flu be prevented? Compare and contrast 2 versions of the vaccine.

• Vaccine- need to get every year (drift)
• Inactivated virus (shot) or live attenuated (nasal)
• Inactivated vaccine induces antibodies, live induces mucosal immunity (no serum antibodies but still effective)
• Both vaccines contain at least one A and B strain
• Prophylaxis after exposure: neuraminidase inhibitors

• The inactivated vaccine delivers viral proteins which are processed via MHC II and induce a humoral immune response (serum antibodies).

• The live attenuated nasal mist induces local viral infection, where viral antigens are processed via MHC I to induce T cell and mucosal immune responses.