Flashcards in Viral Respiratory Infections Deck (79):
What family is Rhinovirus in?
What is the major disease caused by Rhinovirus?
Common cold (rhinitis)
How is rhinovirus transmitted?
Airborne, person to person
Why does rhinovirus preferentially infect nasal epithelium?
Prefers the cooler temperature of nasopharynx (33) than internal body temp (37)
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)
Why is there no vaccine for rhinovirus?
Too many epitopes of the capsid proteins, gives >100 different subtypes
What is the funtion of IRES?
Internal ribosome entry site
In front of each gene, ribosome finds it and starts translation
What are the steps of replication of Rhinovirus?
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
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
What family is Influenza virus in?
Myxovirus - specifically orthomyxoviridae
What are major difference between orthomyxoviridae (influenza) and paramyxoviridae (parainfluenza, measles)?
Ortho - nuclear replication, segmented -sense RNA
Para - cytoplasmic replication, non-segmented -sense RNA
What is the most pathogenic type of influenza? (A, B, or C)
How many segments are in the influenza virion?
How are strains of influenza named?
Type/Place/Number of isolate/Year (Major type of HA and NA)
Example: A/California/07/2009 (H1N1)
What is the mode of transmission of influenza?
Aerosols, direct contact
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
What cells does influenza primarily infect during infection?
Less cilia = less mucus, higher titer virus, more infected cells
What is antigenic drift?
Minor year to year variation that occurs by random mutations in HA and NA
What is antigenic shift?
Major reassortment of gene segments that leads to novel viral allele combination and can lead to increased virulence
What family is Parainfluenza in?
What disease do Parainfluenza type 1, 2, and 3 cause?
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
- Influenza requires acidic pH for fusion, parainfluenza requires neutral pH
- Influenza replicates in nucleus, parainfluenza in cytoplasm
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
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
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)?
Which is more severe, RSV or metapneumovirus?
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?
(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?
What virus is the major cause of the common cold?
What virus is the second most common cause of the common cold?
Where does Rhinovirus preferentially infect?
Nasal mucosa due to lower temperature (optimal for RhV growth)
What receptor does Rhinovirus bind to?
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
What is the incubation period of rhinovirus?
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)
No vaccine (>100 serotypes)
What is the common term for acute laryngotracheobronchitis?
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?
Stridor, hoarseness, fever
What is the incubation period of croup?
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
What respiratory disease is leading cause of childhood hospitalizations for acute respiratory infection?
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?
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
Congenital/anatomic airway defect
What are long term complications of RSV?
Asthma or atopic disease
How is RSV diagnosed?
Nasal specimen for culture
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?
Does and antigenic drift result in pandemic or 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?
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
What are current influenza vaccines directed at (what portion of virus)?
HA portion of virus