HRR: respiratory viruses Flashcards
How can we determine if a virus is active or inactive?
Introduce them to an appropriate host system and look for replication
What are two major structures of viruses?
Naked and enveloped
Describe a naked virus structure.
A protein capsid with genomic material inside
How are naked viruses released?
Via lysis
Describe an enveloped virus structure.
A protein capsid with genomic material inside surrounded by a lipid envelope with embedded proteins
How are enveloped viruses released?
They bud from the plasma membrane or into vesicles that fuse with the plasma membrane
How do enveloped viruses get their membrane?
They steal it from the host via budding
Which virus structure is resistant to inactivation via ethanol?
Naked
Which virus structure is vulnerable to inactivation via ethanol?
Enveloped
What are two main capsid shapes?
Helical and spherical
Which nucleic acid polymerase enzymes are only found in viruses?
RNA-dependent RNA polymerases and RNA-dependent DNA polymerases (reverse transcriptase); they’re used as drug targets
What virus genomes replicate in the nucleus?
ssDNA, dsDNA, retrovirus (RNA)
What virus genomes replicate in the cytoplasm?
dsRNA, -ssRNA, +ssRNA
What virus genome types establish latency/lifelong infection?
DNA and retrovirus RNA
What are nuclear inclusions?
Formed by DNA viruses in cells
Which virus families cause respiratory infections?
Picornaviruses, bocaviruses, coronaviruses, adenoviruses, ortho, and paramyxoviruses
All respiratory viruses are…
Endemic
Most bacterial pneumonias are preceded by…
A viral respiratory infection
Rhinovirus: season and high-risk group?
Year round, NA
Enterovirus: season and high-risk group?
Summer, children
Bocavirus: season and high-risk group?
Unknown, children
RSV: season and high-risk group?
Winter; children, elderly, HSCT recipients
Coronavirus: season and high-risk group?
Year-round, varies
Adenovirus: season and high-risk group?
Year-round, varies
Parainfluenza virus: season and high-risk group?
Type 1 in fall, type 3 in spring; children and HSCT recipients
Influenza: season and high-risk group?
Winter, varies
What are the two categories of picornavirus?
Rhinoviruses and enteroviruses
What is the basic structure of picornavirus?
Small icosahedral, naked, +strand RNA virus
What is the difference between rhinovirus and enterovirus?
Rhinoviruses are acid-labile, meaning they do not survive contact with acid. If they’re swallowed, they’ll be killed in the stomach. Enteroviruses can survive the stomach and thus enter the bloodstream.
What is the main mode of transmission of picornavirus?
Transmission from surfaces
What are the human host cell receptors for HRV-A?
LDLR or ICAM-1
What are the human host cell receptors for HRV-B?
ICAM-1
What are the human host cell receptors for HRV-C?
CDHR3
What is the clinical presentation of picornaviruses?
Common cold symptoms, nasal congestion caused by bradykinin. Lower respiratory tract infection is rare.
Which virus is the most common cause of acute asthma episodes?
Rhinoviruses
Repeated ___ infections increase risk of developing asthma in genetically susceptible people.
HRV-C
How do we treat/prevent picornaviruses?
We don’t; no vaccine and no medications
What is the structure of bocaviruses?
Naked, isohedral, ssDNA genome
Do bocaviruses cause latent infection?
No
Do bocaviruses lead to lower respiratory infection?
Yes, especially in young kids
What are the paramyxoviruses?
Parainfluenza, RSV, measles, mumps, metapneumovirus
How are paramyxoviruses acquired?
The lungs
What is common among the paramyxoviruses?
All acquired through the lungs, all cause viremia, all -ssRNA and enveloped, and all have a fusion protein causing respiratory epithelial multinucleated giant cells
Describe the structure of paramyxoviruses.
-ssRNA enveloped with helical capsid, RNAdpolymerase, glycoprotein spikes, and a lipid membrane stolen from the host
What is the main cause of acute croup (laryngotracheitis) in infants and young kids?
PIV 1
What does PIV 3 cause in very young children?
Severe lower respiratory disease and croup
What is the clinical presentation of parainfluenza?
Abrupt onset of respiratory distress that may sound like a seal barking. It can progress over 1-3 days and may last up to 21 days
What is the prevention and therapy for parainfluenza viruses?
No vaccine, just hygiene; no effective drugs but may use nebulized corticosteroid or epinephrine in severe cases
Describe the structure of RSV.
-ssRNA enveloped genome with attached glycoproteins and fusion proteins that mediates syncytia (death)
Describe the clinical presentation of RSV.
Rhinitis followed by coughing, wheezing, and respiratory distress. Children under 1 may have bronchiolitis and pneumonia
What might you see on x-ray in RSV?
Hyperinflation, hypoxemia, bilateral interstitial infiltrate, perihilar fullness
A young child in the winter has respiratory distress. What is the most likely etiology?
RSV
Describe RSV epidemiology.
25-40% have symptoms of bronchiolitis or pneumonia, and up to 2% are hospitalized
Describe the time period in which we normally see RSV.
November-April with a peak around new years
What is the prevention and treatment for RSV?
Vaccine for older adults and pregnant people 32-36 weeks or palivizumab injection for high-risk children. No specific treatments
What is the clinical presentation of metapneumoviruses?
Basically, same as RSV
How do we diagnose metapneumovirus?
PCR or antigen tests
How do we treat and prevent metapneumovirus?
No treatment or vaccine
Which viruses cause serious disease in HSCT recipients?
Parainfluenza, RSV, hMPV
Describe the structure of coronavirus.
Enveloped +ssRNA genome with peplomer spikes that determine the species and tissue tropism
What is the receptor for SARS-COV-2?
ACE2
Describe clinical presentation of coronavirus.
Common cold in adults and lower respiratory diseases in young children; reinfection is possible
Describe treatment and prevention of SARS-CoV-2.
Vaccines available; drugs include remdesivir, Paxlovid (FDA approved) and molnupiravir
Describe adenovirus structure.
Naked, icosahedral dsDNA genome with pentons that are cytotoxic containing knobs that bind to host cell. The knobs determine tropism
Describe adenovirus epidemiology.
Can cause latency and genome may integrate into host genome. It has a long period of chronic shedding
How can adenovirus spread?
Ocular respiratory, fecal-oral. Super contagious
Describe pathogenesis of adenovirus.
Viremia, persistent viral shedding, and latency
How does adenovirus evade the immune system?
It binds MHC I in the ER to reduce their surface expression and integrates into the genome to become latent
Describe clinical presentation of adenovirus.
Varies, but may present like common cold, pneumonia, pertussis-like illness, conjunctivitis, acute gastroenteritis, and acute hemorrhagic cystitis
What is the most common cause of pink eye?
Adenovirus
How do we diagnose adenovirus?
PCR
What is the treatment and prevention of adenovirus?
No vaccine for prevention, and no standard antiviral treatment though severe systemic disease may respond to cidofovir
Describe pathogenicity of influenza.
Completely depends on the strain and varies by host species!
Describe virulence at the cellular level of influenza.
May see inclusion bodies, syncytia, lysis, cell rounding
Describe the structure of influenza.
Segmented -ssRNA genome. The segments each have a separate helical capsid of RNA binding protein, and each are encased in an envelope
What category does influenza belong to?
Orthomyxovirus
Where does influenza replicate?
The nucleus
Of the 3 influenza types, which one is considered virulent?
Influenza A
What is different about the structure of influenza when compared to paramyxoviruses?
The H and N spikes are separate, dominant, and used for tracking
What is hemagglutinin in influenza A?
An attachment protein that binds host sialic acid. Acidification of it exposes the fusion domain
What is neuraminidase in influenza A?
A detachment protein that cleaves sialic acid
What is M2 in influenza A?
An ion channel that acidifies an endocytic vesicle and enables uncoating; necessary for fusion protein to be exposed
Which influenzas are seen in humans?
H1-3, N1-2
Which influenzas are seen in other animals?
H4-16, N3-9
What is reassortment?
A property associated with influenza in which cells can be infected with two strains at once and thus will produce progeny virions with a mixture of segments from both strains
What is antigenic shift in influenza?
Reassortment; H or N numbers change
What is antigenic drift in influenza?
Point mutations that do not result in H or N number changing
Describe vaccines for influenza.
They’re altered every year to account for antigenic shift and drift
Describe influenza clinical presentation.
Acquired by inhalation and includes a variety of symptoms, notably by CDC symptoms of fever and cough or sore throat
How do we diagnose influenza?
PCR or rapid test
Describe pathogenesis of influenza.
Can cause intense inflammatory response and compromised respiratory epithelium for 2-10 weeks with high susceptibility to bacterial superinfection
What are the 3 causes of death associated with influenza?
- Underlying disease with decompensation (usually heart or lung) 2. Bacterial superinfection leading to pneumonia 3. Severe viral pneumonia and asphyxia (cytokine storm)
What drugs are used against influenza?
- M2 inhibitors (end in -tadine) 2. Neuraminidase inhibitors (end in -mavir) 3. Cap-snatching inhibitor (baxlovir marboxil)
What are vaccine options for influenza?
Quadrivalent whole inactivated virus, nasal trivalent live attenuated virus (2-49 without immune compromise), and high dose quadrivalent whole inactivated virus for those over 65
Distinguish between avian and human influenza.
They bind to different sialic acid residues, avian impacts the lower respiratory tract of humans and human impacts the upper tract. The avian influenza has low transmissibility but high mortality in humans.
