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What are the notable Paramyxoviruses?

This chapter: parainfluenza, Respiratory syncitial virus, human Metapneumovirus



mumps and measles

Paramyxovirus virus (parainfluenza, RSV, hMNV):



basic structure of the virion?


enveloped?


does the nucleocapsid contain the viral polymerase?

Helical


single stranded negative-sense RNA


enveloped


nucleocapsid contains viral RNA transcriptase

Paramyxovirus virus:



steps of the viral replication cycle?


site of replication and assembly?


how are virions released?

1. Entry via receptor binding, fusion.
Replication in the cytoplasm
2. Viral Pol transcribes (+)RNAs


a. viral mRNAs
b. template for (-) genomes
3. Viral proteins synthesized
a. M and GPs inserted in host
cell membrane
4. (-) RNA genomes synthesized
5. Assembly of nucleocapsids (NC).
6. NCs dock at cell membrane and are released by budding.

Paramyxovirus virus replication:



1. Entry via ?
2. ____ transcribes (+)RNAs into?
3. Viral proteins synthesized
a. M and GPs inserted in host
cell membrane
4. (-) RNA genomes synthesized
5. Assembly of nucleocapsids (NC).
6. NCs dock at cell membrane and are released by _______.

1. Entry via receptor binding, fusion.
Replication in the cytoplasm
2. Viral Pol transcribes (+)RNAs


a. viral mRNAs
b. template for (-) genomes
3. Viral proteins synthesized
a. M and GPs inserted in host
cell membrane
4. (-) RNA genomes synthesized
5. Assembly of nucleocapsids (NC).
6. NCs dock at cell membrane and are released by budding.

What additional proteins does RSV have that may be immune system targets? Which one has the highest variability among strains?

F = fusion


G = attachment = highest variability

Parainfluenza virus:



transmission?


populations at highest risk?

Transmission is mostly by contact, fomite or large droplet



< 1y/o at risk for more severe disease

Major disease presentations of parainfluenza virus?

URT = mild disease/cold



LRT = croup, bronchiolitis

Where is the obstruction when you hear:



Inspiratory stridor


Expiratory stridor


Biphasic stridor

Inspiratory stridor = obstruction above the glottis


Expiratory stridor = intrathoracic obstruction


Biphasic stridor = either critical obstruction or an obstruction in the area between the glottis and subglottis.

When do types 1 & 2 parainfluenza have outbreaks? type 3?

Types 1&2 outbreaks in fall and winter



Type 3 is endemic and primary infection occurs early in life

What lab tests are used to diagnose parainfluenza virus?

direct fluorescent antibody test



Rapid identification by direct fluorescent antibody test can distinguish 1, 2, and 3 and has been generally what is relied upon clinically.

What type of cells does parainfluenza infect?


Mechanism of pathogenesis of parainfluenza virus?


1. replicates in epithelial cells of the URT and can spread to LRT


2. IgE increases in pts with LRI; suggests hyperresponsiveness as the cause of symptoms

describe the type of immunity that develops after an infection with parainfluenza virus and whether one can be re-infected and get sick again

Humoral and cell-mediated responses are protective, but transient.



Reinfection is common; infection induces temporary resistance to lower respiratory disease but protection persists < 1 yr and you still get the URI

How does croup present? What is the prodrome? Distinguishing feature(s)?

URI prodrome
Seal bark cough
Intermittent inspiratory stridor wheezing, rales, increased tachypnea

clinical manifestations of bronchiolitis

cough, nasal discharge, and sometimes sudden apnea



Inflammatory obstruction of small airways, epithelial necrosis, mucous plugging, airway narrowing

1. Most common infectious cause of bronchiolitis?


2. Second most common?


3. What else can cause it

1. RSV


2. parainfluenza 3


3. parainfluenza 1&2, adenovirus, influenza, mycoplasma, herpes

How is bronchiolitis diagnosed?

clinical criteria with x-ray findings



rapid viral antigen testing (ELISA +/or fluorescent
antibody techniques permit specific diagnosis)

What are the xray findings in bronchiolitis?

x-ray = hyperinflation, hyperlucency of the
lungs, atelectasis especially RUL

management of bronchiolitis?

hydration and supplemental O2

1. Most common infectious cause of croup?


2. What else can cause it

1. parainfluenza type 1&2


2. adenovirus, influenza, RSV, hMPV,enterovirus, rhinovirus, bacteria

Croup can be diagnosed clinically by what characteristic sign/symptom? What is seen on x-rays?

1. Characteristic seal bark cough


2. Lateral neck film shows widening of the hypopharynx and narrowed subglottic airway.


A-P films shows “steeple sign” of subglottic edema and narrowed airway.

management of croup?

a. Humidification of air by nebulizer.
b. Racemic epinephrine for severe cases.

Transmission of RSV?

human's = only reservoir



contaminated secretions is more important than airborne transmission (Cuddler Study).

Populations at risk for most serious infection with RSV?

Premature babies and those with congenital heart disease or chronic lung disease.

Clinical manifestations in infants

– Bronchiolitis


– Pneumonia


– Croup
– Apnea
– URI
– Otitis media

Clinical manifestations in older children/adults

– URI
– Bronchitis
– Pneumonia (elderly)
– Exacerbation of asthma

Most common clinical manifestation of RSV? physical exam finding?

Bronchiolitis = washing machine breath sounds

When does RSV typically occur during the year

late fall to early spring



In temperate regions, RSV is highly seasonal with gradual onset and decline

How is RSV diagnosed in the lab?

Rapid diagnosis using ELISA, PCR or direct fluorescent antibody test. PCR has become widely adopted.

pathophysiology of RSV?

1. Infects an epithelial cell which causes the formation of a syncytium


2. The infection proceeds deeper into the respiratory tract collecting more debris/cells


3. This will eventually plug small airways = bronchiolitis

Pathologic changes with RSV likely result from _____ and ______

Pathologic changes with RSV likely result from direct viral infection and the host immune response.

Immunity after infection with RSV:


humoral immunity?


cellular immunity?


re-infection?

Cellular response halts established infection; humoral prevents recurrent disease.



repeated infection is common but usually only URI

Treatment of RSV

• Mainly supportive
• Oxygen and ventilation if needed
• Fluids
• Antivirals not generally used, though ribavirin has activity
• Bronchodilators

prophylactic treatment of RSV

Palivizumab = Doesnt prevent infection prevents URI moving into LRI = prevents hospitalization



Humanized murine monoclonal antibody can be given intramuscularly, and is licensed for prophylaxis.

hMPV presents very similarly to

RSV

Diagnosis of hMPV?

Comprehensive Respiratory Platform for PCR now widely available in tertiary hospitals and reference laboratories