Respiratory Viruses Flashcards
Respiratory Viruses
Influenza virus
Rhinovirus
Coronavirus
Parainfluenza virus
Respiratory synctial virus
Metapneumovirus
Adenovirus (sometimes)
Virus families
- Picornaviridae (rhinovirus, coxsackie virus, echovirus, enterovirus)
- Coronaviridae (coronavirus, SARS-CoV)
- Orthomyxoviridae (Influenza A,B,C virus)
- Paramyxoviridae (Parainfluenza virus, respiratory synctial virus, metapneumovirus, measles virus)
Orthomyxovirus
Family:
Genus:
Individual Strain:
Subtypes:
Types:
Family: Orthomyxovirus
Genus: Influenza; Thogotovirus
Individual Strain: A/BAngkok/1/79(H3N2)
Subtypes: Based on hemagglutinin and neuramidase
Types: Based on matrix and nucleoprotein antigens
Antigenic Drift
Minor changes in either the hemagglutinin or neuramidase, or both
- Minor antigenic variations reslut from mutations in hemagglutinin and neuraminidase genes
- The hemagglutinin mutations are primarily found in the four antibody combining sites in the hemagglutinin protein
Major antigenic shift
Occurs infrequently, either hemagglutinin alone or neuraminidase as well. Occurs as a result of gene reassortment between a human and animal strain
Influenza Pathogenesis
- Influenza is an acute respiratory disease
- infects ciliated epithelial cells lining the upper respiratory tract, trachea, bronchi
- Virus replication - destruciton of respiratory epithelium
- Cell damage also due to virus activated CTL
- Viremia - not a major role
Acute influenza infection in adults - symptoms
Rapid onset of fever, malaise, myalgia sore throat and nonproductive cough
Acute influenza infection in children
Acute disease similar to that in adults but with higher fever, GI tract symptoms, otitis media, myositis
Complications of influenza virus infection
Primary viral pneumonia
Secondary bacterial pneumonia
Myositis and cardiac involvement
Neurologic syndromes
Influenza diagnosis
- Clinical signs and epidemiology
- Lab diagnosis
- Rapid antigen capture detects nucleoprotein (15 min)
- rt-PCR
- Hemagglutination/ Serology
- Virus isolation
- Immunofluorescent techniques
Replication and Spread of influenza (7 steps)
- Binding
- Coating/Fusing
- Transcription
- Proteins synthesized
- Replication
- Assembly
- Budding
What is the influenza virus cellular receptor?
Sialic acid
How does the viral membrane fuse with the vesicular membrane inside the cell?
Lowers the pH which triggers fusion and release of contents
Prevention and control of influenza: Immunization
- Formalin inactivated - mixture of prevalent antigenic types
- Attenuated infectious viruses - intranasal administration
- Experimental - DNA vaccines - reverse transcriptase
Prevention and control of influenza: Chemotherapy
- Amantadine and rimantadine - inhibit uncoating by blocking M2 protein
- Ribavirin - inhibits syntehsis of viral RNA
- Zanamivir and Oseltamivir (Tamiflu) neuraminidase inhibitors
Influenza is usually treated with a _______ vaccine
Trivalent
Rhinovirus (characteristics)
- Causes 50% of common colds
- >150 serotypes identified
- Temperature sensitive - grows better at 33º than 37º
- Secretory IgA is most important in limiting reinfection
- Transmission by respiratory secretions
Rhinovirus symptoms
- Headache
- Cough
- Sore throat
- Mucus
- Nasal discharge
All due to inflammatory response
Rhinovirus prevention and control
No effective prevention and control measures to date
- Experimental
- Viral protease inhibitors (Ruprintrivir)
- WIN compounds - block uncoating by inserting in virus surface pore
Rhinoviruses are transmitted via _______
fomites
Coronaviruses (characteristics)
Cause common colds - watery eyes, sneezing, nasal congestion, sore throat
Disesae limited to upper respiratory tract, infects epithelial cells
No vaccine available
Coronavirus Outbreaks
- 2002-2003: SARS outbreak caused by SARS-CoV
- 2012 - acute pneumonia and renal failure MERS-CoV originally named hCoV EMC
Coronavirus - SARS
Fatality Rate:
Transmission:
Source:
Vaccines:
Sudden acute respiratory syndrome
Fatality Rate: 10%
Transmission: Mainly by face-to-face contact; virus in respiratory secretions and feces; not highly contagious
Source: Bats, and other animals sold in markets in China
Vaccines: none currently available
MERS-CoV
Difference from SARS:
First Reported:
Origin:
Cases to date:
Middle East Respiratory Syndrome
Difference from SARS:
- Uses a different cellular receptor
- Does not readily pass from person to person
First Reported: September 2012 (May 2014-US)
Origin: Middle East (nosocomial infections documented)
Cases to date: 400
Paramyxoviridae Family
Morbillivirus
Paramyxovirus
Pneumovirus
Heniparvirus
Paramyxovirus family virus proteins
F: fusion protein
HN: Hemagglutinin virus attachment
Neuraminidase virus release
NS1 and NS2: Nonstructural proteins that modulate the immune response important in vivo
Paramyxoviruses replicate in the ______
cytoplasm
Human Parainfluenza Viruses (HPIV) - key issues
- Common cause of acute and lower respiratory illness in infants/young children/elderly/immunocompromised
- Common cause of croup
- Different types (HPIV1, HPIV2, HPIV3, HPIV4)
- Reverse genetics systems for HPIVs have helped attenuating mutations and to incrementally attenuate
- Vaccines have entered pediatric trials in Phase 1
Paramyxoviridae - Respiratory Synctial virus (RSV)
- 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 elderly
Disease mechanisms of Respiratory Syncytial Virus
- Pneumonia results from cytopathologic spread of virus (including syncytia)
- Bronchiolitis is most likely mediated by host’s immune response
- Narrow airways of young infants are readily obstructed by virus-induced pathologic effects
- Maternal antibody does not protect infant from infection
RSV - pathogenesis
Typical giant cells - pink intracytoplasmic inclusions
Immune response in infants vs adults to RSV
- Infants
- TH2 response
- Mast cell activation
- Eosinophila
- Wheezing
- Adults
- Th1 response - IFN
- Macrophages, NK cells, Cell mediated immunity
- B cells
- Cytolysis
- Antiviral cytokines
- Virus clearance
RSV treatment prevention and control
Otherwise healthy infant:
Premature or immunocompromised infants:
Premature infants:
Vaccine:
Otherwise healthy infant: treatment is supportive, oxygen, IV fluids, nebulized cold steam
Premature or immunocompromised infants: Aerosolized ribarin
Premature infants: Passive immunization with anti-RSV Ig and humanized monoclonal antibodies against viral fusion protein
Vaccine: No vaccine currently available
Human Metapneumovirus - hMPV (Characteristics)
First identified in 2001
Clinical spectrum of disease similar to RSV - most severe in infants, elderly, immunocompromised, those with COPD
Second most common cause of lower RTI in young children
By 5 years of age all children are seropositive
hMPV treatment and prevention
- Most treatment is supportive
- Ribavirin - inhibitory activity against hMPV
- Immunoglobulins
- IVIG
- Humanized monoclonals
- Ribavirin + IVIG
Paramyxoviridae - Hendra and Nipah Virus
Two emerging respiratory viruses with high mortality rates
Have made the apparent jump from bats to people in Australia and Asia
Adenovirus (Characteristics)
- >50 human types identified
- Cause a wide spectrum of disease including respiratory infection
- Conjunctivitis
- GI infections
- Hemorrhagic cystitis
- In respiratory tract, can cause destructive productive infection, persistent infection with virus shedding, or latent infections
In addition to previously mentioned groups, ______ ______ are also highly susceptible to adenoviruses
military recruits
