Viral Respiratory Infections Flashcards by Danielle Himelfarb

What family is Rhinovirus in?

Picornovirus family

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What is the major disease caused by Rhinovirus?

Common cold (rhinitis)

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How is rhinovirus transmitted?

Airborne, person to person

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Why does rhinovirus preferentially infect nasal epithelium?

Prefers the cooler temperature of nasopharynx (33) than internal body temp (37)

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What is the structure of the virion of Rhinovirus?

Non-enveloped, single strand RNA virus
VP1, VP2, VP3 make up capsid
Has IRES (internal ribosome entry site)

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Why is there no vaccine for rhinovirus?

Too many epitopes of the capsid proteins, gives >100 different subtypes

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What is the funtion of IRES?

Internal ribosome entry site

In front of each gene, ribosome finds it and starts translation

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What are the steps of replication of Rhinovirus?

Attaches
Endocytosed in vesicle
Uncoats and releases RNA into cytoplasm
RNA translated in cytoplasm with host ribosomes (targeted to IRES)
Long polyproteins get cleaved by proteases
New vesicles are formed with new viral RNA
Virions form and are released by cell lysis

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What is the host response to Rhinovirus infection?

Induction of chemokines and cytokines that recruit inflammatory cells
Airways respond by contracting, increasing in mucus, increasing inflammation

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What family is Influenza virus in?

Myxovirus - specifically orthomyxoviridae

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What are major difference between orthomyxoviridae (influenza) and paramyxoviridae (parainfluenza, measles)?

Ortho - nuclear replication, segmented -sense RNA

Para - cytoplasmic replication, non-segmented -sense RNA

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What is the most pathogenic type of influenza? (A, B, or C)

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How many segments are in the influenza virion?

8 segments

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How are strains of influenza named?

Type/Place/Number of isolate/Year (Major type of HA and NA)

Example: A/California/07/2009 (H1N1)

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What is the mode of transmission of influenza?

Aerosols, direct contact

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What are the steps of replication of influenza virus?

HA binds to sialic acid on surface of cell
Virus is endocytosed and endosome acidified
Acidic environment causes conformational change in HA, causing it to fuse with membrane and release viral RNA into cytoplasm
Viral RNA goes to nucleus for replication
Viral RNAs exported from nucleus and translated
New virions made, bud from cell

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What cells does influenza primarily infect during infection?

Ciliated cells

Less cilia = less mucus, higher titer virus, more infected cells

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What is antigenic drift?

Minor year to year variation that occurs by random mutations in HA and NA

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What is antigenic shift?

Major reassortment of gene segments that leads to novel viral allele combination and can lead to increased virulence

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What family is Parainfluenza in?

Paramyxoviruses

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What disease do Parainfluenza type 1, 2, and 3 cause?

Croup

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What is a major similarity and a major difference in the virion/genome of Influenza and Parainfluenza?

Similarity: Both contain own polymerase that starts working to replicate virus right when it enters cell

Difference:

Influenza requires acidic pH for fusion, parainfluenza requires neutral pH
Influenza replicates in nucleus, parainfluenza in cytoplasm

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What are the steps of replication of parainfluenza?

Virus binds sialic acid on surface of cells
Fusion occurs at neutral pH
Viral mRNA is transcribed in cytoplasm
Proteins are processed in ER and Golgi
Virions bud from cell

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How does parainfluenza block innate immune response?

Like other paramyxoviruses, can inhibit induction of interferon or degrade the proteins that turn on interferon induced genes

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What is the mode of transmission of Parainfluenza?

Aerosols, direct contact

What virus causes most serious pediatric respiratory infections?

RSV (respiratory syncytial virus)

What is the structure of the virion of RSV and metapneumovirus?

Nucleocapsid in lipid envelope | Also contains own polymerase (like influenza and parainfluenza)

Where do RSV and metapneumovirus replicate (cytoplasm or nucleus)?

Cytoplasm

Which is more severe, RSV or metapneumovirus?

RSV

What is the cause of the severity of RSV?

Starts in nasopharynx and disseminates to lower respiratory tract Causes necrosis and destruction of bronchiolar epithelium and ciliated epithelial cells Causes influx of inflammatory cells, mucus production, and cell debris that can block bronchioles

What animal causes SARS?

Civet cats | civets got from bats, which are the reservoir

What animal causes MERS?

Camels? Bats? Dunno

What protein does SARS bind to?

ACE2 on surface of ciliated epithelial cells

What protein does MERS bind to?

DPP4 on surface of clara and type 2 alveolar cells

What is the major determinant of immunogenicity in SARS and MERS?

Spike protein

What virus is the major cause of the common cold?

Rhinovirus

What virus is the second most common cause of the common cold?

Coronaviruses

Where does Rhinovirus preferentially infect?

Nasal mucosa due to lower temperature (optimal for RhV growth)

What receptor does Rhinovirus bind to?

ICAM1

How does Rhinovirus cause the symptoms in the nasal mucosa?

Induces production of bradykinin - causes vasodilaiton | Induces production of IL-8 - causes influex of PMNs and vascular permeability

What is the typical clinical presentation of rhinovirus infectoin?

Sneezing, rhinitis, nasal obstruction, sore throat | NO fever

What is the incubation period of rhinovirus?

24-72 hours

When do rhinovirus infections typically peak?

Two peaks: fall and late spring

How is rhinovirus transmitted?

Direct contact or respiratory droplets

What is the treatment for rhinovirus?

``` No approved anti-virals Supportive care (hydration, antihistamines) Intranasal corticosteroids Zinc, echinacia No vaccine (>100 serotypes) ```

What is the common term for acute laryngotracheobronchitis?

Croup

What is the leading viral cause of croup?

Parainfluenza viruses (usually PIV-1 or PIV-3)

What is the hallmark of croup?

inflammation and subsequent narrowing of subglottic region of trachea, causing "barking cough"

In what populations is parainfluenza virus more of a problem?

Young children, elderly, immunocompromised | May need intubation

What is the clinical presentation of croup?

Barking cough | Stridor, hoarseness, fever

What is the incubation period of croup?

1-7 days

How is croup transmitted?

Direct contact, respiratory droplets

What is the seasonality of PIV-1?

Autumns of odd numbered years

What is the seasonality of PIV-2?

Annual in autumn (only mild disease)

What is the seasonality of PIV-3?

Annual in spring and early summer

How is croup diagnosed?

Naso-pharyngeal specimen submitted for viral culture, antigenic testing, or PCR Can do neck x-ray to assess tracheal narrowing ("steeple sign")

What is the therapy for croup?

No approved anti-virlas Supportive care Monitor airway No vaccine

What respiratory disease is leading cause of childhood hospitalizations for acute respiratory infection?

Bronchiolitis

What is most common viral cause of bronchiolitis?

Respiratory Syncytial Virus (RSV)

How does RSV cause airway obstruction?

Infects nasopharynx and spreads to bronchiolar epithelium, including pneumocytes Syncitia formation promoted by F (fusion) protein Necrosis and inflammation leads to small airway obstruction Severe disease can cause respiratory failure

What is the clinical presentation of bronchiolitis?

Fever, wheezing, increased respiratory effort, apnea

What is the incubation period of bronchiolitis?

4-6 days

When is the peak of transmission of RSV?

Winter: January- February

What are risk factors for development of severe RSV?

``` Premature birth (<12 weeks Chronic pulmonary disease Congenital heart disease Immunodeficiency Neurological disease Congenital/anatomic airway defect ```

What are long term complications of RSV?

Asthma or atopic disease

How is RSV diagnosed?

Nasal specimen for culture Antigenic testing PCR Chest x-ray and pulse ox to assess pneumonia and oxygenation status

What is the treatment for RSV?

Supportive care +/- steroids and bronchodilators Severely ill have been treated with Ribavirin Palivizumab: monoclonal antibody against RSV, approved for immuneprophylaxis for high-riskinfants

What area of the respiratory tract does influenza effect?

All of it

Does an antigenic shift result in pandemic or epidemic?

Pandemic

Does and antigenic drift result in pandemic or epidemic?

Epidemic

What is the clinical presentation of influenza?

Abrupt *fever*, severe headache, severe myalgia, severe malaise + Respiratory symptoms +/- GI symptoms

What is the incubation period of influenza?

3 days

What is the seasonality of influenza?

Winter in respective hemispheres | constant low level in tropics

What age group is predominantly afflicted by influenza?

Elderly, immunocompromised, young

What is the shape of the mortality curve of seasonal influenza?

U shape (skew to older)

What is the shape of the mortality curve of pandemic influenza?

W shape (young otherwise healthy adults get infected)

How is influenza diagnosed?

Rapid antigen tests | PCR

What are current influenza vaccines directed at (what portion of virus)?

HA portion of virus

What are current drugs used to treat influenza?

Neuraminidase inhibitors - Oseltamivir - Zanamivir - Peramivir

Viral Respiratory Infections Flashcards

(79 cards)