15 - Respiratory Viruses Flashcards
What are viruses that have respiratory transmission?
Influenza virus Rhinovirus Coronavirus Parainfluenza virus Respiratory syncytial virus Metapneumovirus Adenovirus
What is the path that a respiratory virus takes?
Replicates in the URT and causes upper and sometimes lower respiratory infections and disease.
What illnesses is respiratory syncytial virus associated with?
Pneumonia
Bronchiolitis
Bronchitis
Causes severe illness in infants.
What viruses are picornaviruses and are involved in respiratory disease?
Rhinovirus
Coxsackie virus, echovirus, enterovirus.
What viruses are in the coronaviridae family and are involved in respiratory disease?
Coronavirus, SARS-CoV, MERS-CoV
What viruses are in the orthomyxoviridae family and are involved in respiratory disease?
Influenza A, B, and C virus
What viruses are in the paramyxoviridae family and are involved in respiratory diseasE?
Parainfluenza virus, respiratory syncytial virus (RSV), metapneumovirus, hendra and nipaviruses, and measles virus
What are the subtypes of Influenza A (orthomyxo)? What are they based on? What are the types (A, B, C) based on?
Species (subtypes): H1N1, H2N2, H3N2 - based on HA and NA
Types (A, B, C) : based on matrix and nucleoprotein antigens.
What is the structure of influenza virus? What is it’s genome like?
HA and NA on the surface.
M2 ion channel and M1 matrix protein
- ssRNA virus with 8 segments
RdRp
What is the difference between antigenic drift and antigenic shift (time-wise)?
Drift: slow changes that take a long time
Shift: rapid change
What is antigenic drift? What does this result in?
Minor changes in either HA or NA (or both) that results from mutations in HA or NA genes.
The HA mutations are mainly found in the four Ab combining sites in the HA protein.
Causes EPIdemics
What is major antigenic shift?
Occurs infrequently in either HA alone or with NA.
Result of gene reassortment between human and animal strains.
Results in PANdemics.
What is the origin of H1N1?
Only protein whose origin was human was the PB1 protein.
All others were from birds or swine.
What is the pathogenesis of influenza?
Acute respiratory disease that infects ciliated epithelial cells lining the URT, trachea, and bronchi.
Virus replication and virus activated CTL (cytotoxic T lymphocytes) destroys resp epithelium
Viremia is NOT a major role in pathogenesis.
What is the pathogenesis of influenza A? What causes the symtpoms?
- Replication in resp tract and desqaumation of mucus-secreting and ciliated cells
- Influenza syndrome:
-Interferons and cytokines are what cause flu like symptoms
-destruction of the epithelial cells are what set people up to secondary bacterial infections (
like pneumonia)
What is the time course of Influenza A infection?
Time between exposure and symptoms is very short, just a few days.
What are symptoms of acute influenza in adults? What about children?
Adults: Rapid onset of fever, malaise, myalgia, sore
throat, and nonproductive cough
Children: Acute disease similar to that in adults but with
higher fever, GI symptoms
(abdominal pain, vomiting), otitis media, myositis, and more frequent croup
What is the most common complication of influenza virus?
Secondary bacterial pneumonia.
Also can occur:
- primary viral pneumonia
- myositis (muscle inflamm)
- Cardiac involvement
- neurologic syndromes
How do you diagnose someone with influenza?
Laboratory diagnosis:
- rapid antigen capture, detects nucleoprotein (NP) of both influenza A and B viruses in about 15 min
- rt-PRC
What is the influenza virus cellular receptor? What occurs after attachment?
Sialic acid is the viral protein receptor that HA binds to.
After attachment virus is brought into the cell. You need the viral envelop to fuse with the endoscope and this is done by decreasing the pH.
What are the immunization methods for influenza?
- Chemically inactivated - mixture of prevalent antigenic types (hemagglutinin and neuramindase)
- attenuated infectious viruses
→ intranasal administration
What are three ways that influenza can be treated?
- amantadine and rimantadine - inhibit uncoating by blocking M2 protein
- ribavirin - inhibits synthesis of viral RNA
- Zanamivir (Relenza) and Oseltamivir (Tamiflu) are neuraminidase inhibitors (most common)
What causes 50% of the common cold? Describe this virus? What are the symptoms and what are they caused by?
Rhinovirus - picornavirus w/ replication and structure similar to polio.
> 150 serotypes-human only
SymptomsL headache, cough, sore throat, nasal discharge. Due to inflamm response release of bradykinin and histamine in the nose.
How is rhinovirus transmitted? What limits re-infection? What is it sensitive to?
Temperature sensitive - grows better at 33° than 37°
Secretory IgA most important in limiting re-infection
Transmission by respiratory secretions directly from individual to individual or through fomites
What virus is the second leading cause of the common cold (10-15%)? What are symptoms and what is this illness limited to?
Coronavirus: watery eyes, sneezing, nasal congestion, sore throat, sometimes fever, chills, headache, cough.
Limited to URT, infects epithelial cells and has an optimal temp of 33 to 35 C.
Coronaviruses normally just cause a cold, BUT which two members of the coronavirus family are associated with serious disease? Is a vaccine available?
Sudden Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)
No vaccine
What is the fatality of SARS and how is it transmitted? What are likely sources? What did it last re-emerge?
About 10% fatality
Face-to-face contact, virus in resp secretions and feces. NOT highly contagious.
Likely sources: bats and other animals sold in markets in china. Has not re-emerged since 2003.
When was MERS first reported? How was it differentiated from SARS? How is it spread?
Sep 2012 in middle east; uses a different cellular receptor than SARS.
Can infect bats and camels.
Not efficiently passed from person to person b/c RNA virus and genetically unstable.
What is the result of MERS? When and where was the first US case?
Serious cases tend to have underlying conditions.
Nosocomial infections documents and still birth documented.
First US case in 2014 in indiana.
What human pathogens are in the paramyxoveridae family and cause respiratory infections?
Measles virus
Parainfluenza viruses 1-4
Mumps
RSV
Metapneumovirus
Hendra
Nipah
What is the structure of paramyxoviruses?
- ssRNA
Fusion protein for entry,
HN hemogluglutinin for attachment, and neuraminidase for release. (not present in RSV)
NS1 and NS2 are non-structural proteins that modulate the immune response.
What is caused by human parainfluenza virus (HPIV)?
Common cause of acute upper and lower respiratory illness in infants, young children, the elderly and the immunocompromised.
What are the different types of human parainfluenza virus (HPIV)? What illness is each associated with?
HPIV3 is similar to respiratory syncytial virus (RSV) in that it is a common cause of lower respiratory illness, such as bronchiolitis, in the first year of life.
HPIV1 and HPIV2 tend to infect later in life than HPIV3 and are a common cause of croup.
HPIV4 usually asymptomatic or mild disease.
What does respiratory syncytial virus (RSV), a paramyxovirus, cause? Who does it infect?
Most common cause of fatal acute respiratory tract infection in infants and young children.
Infects virtually everyone by age 2.
Re-infections occur throughout life, can be severe in the elderly.
What is the disease mechanism of RSV? What can result from infection?
Virus causes localized infection of respiratory tract (Virus does not cause viremia)
- Pneumonia results from cytopathologic spread of virus
- Bronchiolitis is most likely mediated by host’s immune
response. - Narrow airways of young infants are readily obstructed by
virus-induced pathologic effects.
Does maternal antibodies protect infants from getting RSV? Does natural infection prevent reinfection?
Maternal antibody is insufficient to protect infant from
infection, but it can makes the infection less severe.
Natural infection does not prevent re-infection.
What is the pathogenesis of RSV?
Giant cells become infected with RSV and you will see pink intracytoplasmic inclusions.
Fusion proteins are make and cause giant cells to stick together - resulting in multinucleated giant cells.
When the giant cells die they slough off and that can block the airway made worse by
inflammation due to infection!
What Immune response occurs in infacts with RSV?
Th2 activates IgG and IgG causing mast cell activation.
Th2 also activates IL4 and 5 which causes eosinophilia.
This causes prostaglandin D2 and histamine release resulting in wheezing.
How should you treat an otherwise healthy infant with RSV?
treatment is supportive, oxygen, IV fluids, nebulized cold steam.
No vaccine available.
How should you treat a premature or immunocomp infant with RSV?
Aerosolized ribavirin, passive immunization with anti-RSV Ig and humanized monoclonal antibodies against viral fusion protein.
No vaccine available.
What is the clinical spectrum of disease associated with human metapneumovirus (hMPV)?
Clinical spectrum of disease similar to RSV, with the most
severe disease seen in infants, the elderly, the immunocompromised, and in patients with pulmonary
disease and COPD
Second most common cause of lower RTI in young children after RSV
By age ____, essentially all children are seropositive for human metapneumovirus (hMPV)?
5 yrs
What is the treatment for metapneumovirus?
To date treatment is mainly supportive:
• Ribavirin – inhibitory activity against hMPV
• Immunoglobulins
Vaccine strategies likely to be different for young children and elderly adults.
What diseases are associated with adenovirus? How many types are there in humans?
> 50 human types identified
Wide spectrum of disease including respiratory infection (pharyngitis), conjunctivitis (pinkeye), gastrointestinal infections, and hemorrhagic cystitis (inflammation of the urinary bladder.
What can adenovirus respiratory infections lead to? What does adenovirus do in the respiratory tract?
Viremia
In respiratory tract, can cause destructive productive infection,
persistent infection with virus shedding, or latent infections in
lymphoid tissues like tonsils or adenoid tissue
Systemic infections in immunocompromised patients
How does adenovirus spread within the body>
Replicates initially in the upper respiratory tract; Sometimes it just stops there and infects there, but sometimes it moves on and infects other organs.
