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107 Cards in this Set
- Front
- Back
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What are some diseases of the respiratory system?
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Lung cancer
Asthma TB |
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What is the impact of respiratory diseases on human health?
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Responsible for 10% of hospitalization and 16% of deathes in Canada
Responsible for 18% of mortality in kids under 5 (15% by diarrhea) Lung cancers= 15% of all cancers, responsible for 29% of all cancer deaths |
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How many ppl does asthma affect?
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300 million worldwide (6-7% of the population)
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How many ppl does TB affect?
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1.8 million deaths
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How many deaths do acute infectious respiratory disease cause per year?
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3-4 million
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What are the different types of respiratory infection?
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Upper resp tract infection (URTI)
Lower resp tract infection (LRTI) |
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What are the symptoms of URTI?
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Coryza (congestion)
Cough, hoarsness, rhinitis (runny nose) Pharyngitis (sore throat) Fever Poor feeding |
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What are the symptoms of LRTI?
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Occurs to 1/3 of infants with resp traact infections
Tachypnea (rapid breathing) Wheeze, severe cough, breathless, respiratory distress |
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Which is more severe?
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LRTI
--> 1-2% of LRTI infants need hospitalization |
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Which tests can be done for viral diagnosis?
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Virus culture
Serology Ag detection RT PCR |
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What are factors that influence the susceptibility to and severeness of viral resp diseases?
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Genetic factors
Immune factors Viral factors Physical factors |
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What are the genetic factors that do this?
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Genes involved in:
Type of IR Magnitude of IR Limiting viral load -->Works on T cells and immunopathology and viral induced damage |
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What are the immune factors involved?
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Immunosuppressed/hyporesponsiveness
Lack of previous exposure/immune memory Reduced innate IR Reduced adaptive IR -->Works on immunopathlogy and viral induced damage |
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What do viral factors do to cause severeness of resp disease?
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Inhibition of type I IFN
Increased exposure to virus -->Viral induced damage |
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What are the physical factors that may lead to inc severity?
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Mostly for children:
Small body size Limited E reserves Small airways -->reduction of gaseous exchange |
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What does this all lead to?
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Respiratory compromise
-->Disease |
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How is disease caused?
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Directly destroy cells (viral induced damage)
IR responds and damages host cells |
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How is viral resp disease clinically managed?
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Antivirals
Vaccines Antibiotics Bronchodilaters Corticosteroids O2 supplementation, nasal/gastric tube feeding, IV fluids, nasal bi-lvl positive airway P (BiPAP), mechanical ventilation Hypertonnic saline inhalation |
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What are examples of bronchodilaters?
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B2 agonist
Nebulozed epinephrine ipatropium bromide |
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What are some viruses that cause resp tract infection?
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Resp syncytial virus (RSV)
Rhinovirus Influenza Adenovirus Coronavirus Enbterovirus Reovirus Human metapneumovirus Parainfluenza virus Bocavirus Poluomavirus |
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Which virus is the main cause of hopitalization due to bronchiolitis?
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Respiratory synctial virus
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What kind of a virus is rhinovirus (RV)?
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Smallest virus
Belongs to Picornaviridae Non-enveloped + ssRNA |
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How big is RV?
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30 nm in diameter
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How many serotypes does RV have?
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99 serotypes
hRV-A (73) hRV-B (26) |
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What are the receptors of RV?
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ICAM-1 (mostly)
LDLR (low-density lipoptn; minor) |
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Who does RV infect?
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Infects all ages
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What disease does RV cause?
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~1/2 of all common colds
->symptoms resolve ~ 1 week |
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What is the tissue tropism for RV?
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Respiratory epithelium
Local infection |
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Is there a cure for this virus?
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No antivirals
No vaccine ->Life cycle similar to poliovirus (also a picornaviridae) |
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What kind of a virus is Coronavirus?
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A Coronaviridae
Enveloped virus +ssRNA virus |
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What is the size of a coronovirus?
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80-200 nm in diameter (bigger than RV)
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What kind of disease does coronavirus cause?
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10-30% of all common colds
Half the infections are asymptomatic |
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Where does coronoavirus infect?
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Upper resp tract
GIT |
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Where are the coronovirus viral particles assembled?
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At the golgi
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Which other virus is part of coronaviridae?
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SARS
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Describe Adenovirus
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Part of Adenoviridae
Non-enveloped Icosahedral particles dsDNA genome (linear) |
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What is the size of adenovirus?
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80-100 nm (same size or a little smaller than coronovirus)
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What infections does this cause?
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3-5% of acute res[ omfection in kids
2% in adults -->Also causes resp illness, gastroenteritis, hepatitis, Reye's syndrome |
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How many serotypes does adenovirus have?
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50 + serotypes
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Describe the Reovirus
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Part of reoviridae
10 segments of dsRNA (Rota has 11 segments) Non-enveloped Icosahedral virus |
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What is the size of Reovirus?
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65-70nm
Smaller than Coronavirus/Adeno, but larger than RV |
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Where does Reovirus infect?
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Resp tract
Gut |
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Does Reovirus cause disease in these places?
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No
--> .: can be used as a vector for gene therapy |
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Describe Parainfluenza virus
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Part of Paramyxoviridae
Enveloped Pleomorphic (some VP spherical, others linear) -ssRNA (linear) |
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What is the size of the Parainfluenza virus?
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150-200 nm
->Same size or larger than the coronavirus |
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What ptns does the parainfluenza virus carry?
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Hemagglutinin
Neuraminidase |
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What does parainfluenza virus cause?
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75% of the cases of croup
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What treatment is available for parainfluenza virus?
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No vaccine, no antivirals
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When was Respiratory synctial virus first isolated?
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1956
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What is the reservoir for RSV?
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Human origin
No anima; reservoir |
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Are there animal versions of this virus?
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Yes, bovine RSV and pneumonia of mice
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Who does RSV infect?
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2/3 of infants infected in their 1st year
90% infected 1+ times by the time they're 2 Affects elderly and immunocompromised |
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How many infections are there worldwide?
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64 million infections/year
160,000 deaths |
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What is the treatment for RSV?
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No vaccine
No antivirals |
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Describe RSV
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Paramyxovirus family
Enveloped virus 1 copy of (-) ssRNA Pleomorphic, spheres and filaments |
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What is the rote of infection for RSV?
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Aerosol
Direct contact Inoculation sites: nose and eyes |
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What is the 1ry site of RSV infection?
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Nasopharynx
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What are the symptoms of RSV infection?
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Cough, fever, bronchiolitis, air trapping, wheezing, pneumonia
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What pathology does RSV cause?
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Necrosis of epithelial cells of resp tract (patchy)
Infiltrates of monocytes and T cells, neutrophils Mucous secretion |
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What is the infectivity of RSV?
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High: one of the most contagious human pathogens
Natural intro of RSV can cause more than 90% of infants and children infected in daycare |
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How does RSV compare to Influenza?
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RSV is less invaasive and less pathogenic than influenza
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Why is this so?
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RSV is limited in Antigenic and strain diversity
-->Only one serotype |
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When does RSV infection occur?
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Very early in life
Peak hospitalization of RSV infection at 2 months of age |
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What can RSV do?
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Re-infection
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What are the target cells of RSV?
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Superficial cells of respiratory epithelium
->Eventually, cells will die and get damage to the resp tract |
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How does RSV increase its diversity?
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Heavy Glycosylation of G ptn
Secreted G ptns protect viruses from neutralizing (80% sG vs virion ass't G ptn) ->2 types of G ptns, 1 secreted, 1 not |
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How is the secreted G ptn made?
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From Tl of 2nd meht
Soluble, not mb bound .: can go around |
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What does the tissue tropism of RSV do?
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Reduces the effectiveness of host immunity
Local IgA responses are short lived Inefficient access of serum Ab to respiratory lumen |
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What happens to the Tcyt that are recruited to the lungs?
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Fctnally impaired virus specific CD8+ Tcyt (.: no CMI)
Delay presentation of RSV Ag to the immune system, beccause inner lumen of host hidden at first |
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What is another cause of reinfection?
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Immunological immaturity at infancy
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Why is the host IR reduced in effectiveness in RSV infection?
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RSV infects epithelial cells in inner resp cells
Don't get a strong local IgA response (short lived compared to IgG in the blood) Ab in the blood are very good at maintaining resp infection |
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Describe the structure of RSV
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Has many ORFs
Enveloped spikes Nucleocapsid Matrix (inner env) |
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Which ptns are on the surface of the envelope?
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Fusion ptn and G ptn
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What is the G ptn for?
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Attachment
Neutralization and protective Ag Ab decoy (secreted G) Fractalkaline mimic TLR antagonist |
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What is the F ptn for?
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Fusion and entry
Neutralization and protective Ag TLR4 agonist Putative viroponn Inhibits apoptosis** |
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What are the nucleocapsid ptns?
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N: RNA binding
P: Phosphoptn, how to get to Pol E: Polymerase M2-1: Transcription processivity factor |
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What ptn makes up the inner envelope?
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M: Matrix ptn, needed for assembly
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What are the regulatory ptns of RSV?
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M2-2
Decreases viral T Inc RNA replication |
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What are the nonstructural ptns?
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NS1: inhibit type I IFN induction
NS2: Inhibit type I IFN signalling, activated PI3K and NF-kB, inhibit apoptosis |
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What are the 3 ptns of the env?
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G, F, Sh
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How does RSV compare to Influenza?
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RSV is less invaasive and less pathogenic than influenza
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Why is this so?
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RSV is limited in Antigenic and strain diversity
-->Only one serotype |
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When does RSV infection occur?
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Very early in life
Peak hospitalization of RSV infection at 2 months of age |
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What can RSV do?
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Re-infection
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What are the target cells of RSV?
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Superficial cells of respiratory epithelium
->Eventually, cells will die and get damage to the resp tract |
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Where is the viral genomic RNA?
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In the matrix
Bound by viral nucleoptn and enz needed to replicate the viral RNA |
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Describe teh life cycle of RSV
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1) Attaachment of virus to host cell surface
G ptn binds viral receptor on host 2) After attachment, viral RNA injected into the cytoplasm and starts T to make viral Pol, etc 3) Viral genomic RNA replicated F ptn can cause fusion to neighbouring cells |
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What is the cellular receptor for parainfluenza virus?
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HN binds sialic acid
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What is the cellular receptor for measles virus?
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H binds CD46 or SLAM
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What is the cellular receptor for Hendravirus?
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G ptn binds to ephrinB2 and EphrinB3
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What is the cellular receptor for hRSV?
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G ptn binds to heparin or proteoglycans
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What is the receptor for flu?
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Sialic acid
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What happens after RSV enters the cell?
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Virus carries -ssRNA .: can't be used immediately by cell ribosomes .: needs to carry its own viral Pol
T viral RNA into |(+) mRNA Made into many fragments of viral mRNA (each carries 1 ptn) Shift from T into mRNA into antigenome ->Full length +ssRNA which will be made into more (-) stran RNA This can be pckged |
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Describe the intergenic sequence of RSV
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GE 1-56 NT GS
(GS= gene start) (GE= Gene end) |
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What are the GE and GS seq?
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Very short RNA seq
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What is the intergenic seq for?
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RNA pol attaches to the 3' end of +ssRNA, starts T, then slides
When it reaches GE, stops making RNA Then sllides on 1-56 nt, hits GS and starts T again, makes more RNA |
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What happens at the M2/L overlap?
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The GS is 1st this time
Pol goes past GS, stops at GE (.: completes M2) Then slides back 46 nt to GS and makes L RNA (for Pol) |
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Describe what RSV Pol does
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Binds the leader sequence at the 3' end
Falls off before it reaches the 5's end Genes closer to the 3' end have higher abundances because Pol falls off towards the 5' end |
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Why does Pol use this mechanism?
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Mechanism used to control how many ptns are made
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Describe how virus infection is detected
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Innate immunity is important
Make a lot of cytokines (including IFN) Use RIG-I or Mda5 to rec'g virus Trigger cascade of signal transduction Ends by the release of factors Factors enter the nucleus, bind and cause T of cytokines These go and bind their receptors on a different cell |
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What does IFN trigger?
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Another singal cascade
->Stat1/2 (TF) which go back to nucleus, binds promoters of some genes (IFN-stimulated genes) Play a role in innhibition of viral replication |
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What are the sensors used to detect RSV?
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RIG-I
TLR2/6, TLR-4 (at cell surface) In the endosome: TLR3 |
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What happens if viral RNA binds recceptors?
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Trigger signal paths, make cytokines and protect cells
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How do viruses counteract these cytokines?
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Inhibit Mda5 and RIG-I path using NS2
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What does NS2 do?
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Prevents NF-kB modification and also stops Stat-1/2 from promotin more gene expressioin
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Is parainfluenza virus the same as influenza?
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No
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What is the major cause of resp disease in young children?
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Resp synctial virus
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