Lec 25 Resp Viruses Flashcards
What does palivizumab treat?
RSV infections
What does ribavirin treat?
RSV infections
What does cidofivir treat?
adenovirus infection
What are the respiratory viruses we are responsible for?
Parainfluenza (hPIV) Respiratory Syncytial Virus (RSV) Metapneumovirus (hMPV) Influenza Coronavirus (hCoV) Adenovirus Rhinovirus
What type of virus is measles?
morbillivirus
what type of virus is parainfluenza?
paramyxovirus
What type of virus is respiratory syncytial virus [RSV]?
pneumovirus
What type of virus is metapneumovirus?
pneumovirus
Paramyxoviruses: what sense, strandedness, DNA/RNA?
- negative sense
- single stranded
- non-segmented RNA
What are the 3 proteins of paramyxovirus nucleocapsid?
helical nucleocapsid with 3 proteins
- nucleoprotein [NP]
- polymerase phosphoprotein [P]
- large protein [L]
What are the glycoproteins in the lipid bilayer of paramyxoviruses?
- fusion protein [F]
- attachment proteins [HN, H, G]
How do paramyxoviruses replicate?
- attachment proteins bind to sialic acid on cell surfaces
- genome transcribed into individual mRNAs and full-length + RNA template
- nucleoplasmid associated with matrix and plasma membranes and leaves by cell budding
What are the clinical symptoms of parainfluenza virus?
- primarily in young children get upper and lower respiratory tract infections
- –> croup, common cold, bronchiolitis, pneumonia
- community acquired resp tract infection in adults
What are the types of parainfluenza virus that most commonly cause croup?
HPIV-1, HPIV-2
What is pathogenesis of parainfluenza?
- infects nasal and pharyngeal mucosal epithelia
- spread locally along respiratory epithelium to larynx and trachea
What is the steeple sign?
narrowing of trachea in subglottic region
= sign of croup
How is parainfluenza transmitted?
respiratory droplets or direct person-person contact
When do serotypes 1-4 infections occur primarily
HPIV-1 and HPIV-2: fall
HPIV-3: through year, peak in spring
HPIV-4: no well-defined infection pattern
How is parainfluenza diagnosed?
- antigen detection: direct fluorescent antibodies [DFA] or ELISA
- cell culture
- PCR
What is treatment for parainfluenza?
normally self-limited, give supportive treatment
What is treatment for croup?
- IV/IM/oral dexamethasone [steroid]
- for more serious: nebulized racemic epinephrine
What are clinical syndromes of RSV virus?
- bronchiolitis or pneumonia [most common cause of bronchiolitis in kids < 2 yrs old]
- usually upper respiratory tract disease
- lower respiratory diseases in older children and adults
Who is at increased risk for severe RSV?
- preterm birth
- congenital heart diseases
- chornic lung disease of prematurity
- immunodeficiency
How is RSV transmitted?
- by direct contact with contaminated secretion or fomite, persist on environmental surfaces/hands for hours
When are RSV outbreak?
- winter and early spring in temperate climates
How is RSV diagnosed?
rapid antigen test [fast but not that sensitive]
also: DFA, cell culture, PCR
What is treatment for RSV? for not severe? for severe?
if not severe: supportive
if severe/immunocompromised: ribavirin [oral, IV, aerosolized forms]
What is ribavirin? mech of action? what is downside?
- nucleoside analog that inhibits nucleic acid synthesis
- used to treat RSV
- comes in oral/IV/aerosolized form
- its a teratogen so can’t be administered near pregnant women in aersolized form
What are ways to prevent RSV?
- give palivizumab = monoclonal antibody against RSV F protein
- infection control = use contact precautions
What is palivizumab?
- monoclonal antibody against F protein of RSV
- gives passive immunity to high risk infants
- reduces hospitilization rates
- give monthly IM during peak season [nov - march]
What is pathogenesis of RSV?
- replicates in nasopharynx then infects bronchiolar epithelium
- extends to alveolar pneumocytes by cell-cell spread, aspiration of secretions, formation of syncytia!!!
- necrosis of bronchi and bronchioles causes mucus plugs to form
What are the first and second leading cause of bronchiolits in infants?
first: RSV
second: human metapneumovirus
What are clinical syndromes associated with human metpneumovirus?
- bronchiolitis in infants
- 15% of common colds in children
- pneumonia, croup, URIs
Who is at risk for severe hMPV?
- immunocompromised
- preterm birth
- transplant
- cardiopulmonary disease
How is human metapneumovirus [hMPV] transmitted?
- direct or close contact with contaminated secretions
- some health-care associated infections
When do hMPV infections occur?
late winter/early spring in temperate climates
how is hMPV diagnosed?
PCR
antigen detection
cell culture [but difficult to grow and requires long incubation]
What is structure of coronavirus?
- enveloped
- single strand
- positive sense
- RNA
- glycoproteins form halo-like projections that surround envelope = corona
- RNA genome plus N protein form helical nucleocapsid
How if hMPV treated?
supportive
How is coronavirus replicated?
- uses E1/E2 attachment proteins to bind cell
- virus fuses with cell and genome is released in cytoplasm
- translation of genome in two phases
- —- early phase: produces RNA polymerase
- —- late phase: negative sense RNA yields struct and non struct protein
- forms into vesicle at RER
- released by exocytosis
What clinical syndromes associated with coronavirus?
- common cold and other resp infections
- gastroenteritis
- SARS
What are signs of SARS? possible cause?
- can be due to coronavirus
- fever, pneumonia/resp distress, diarrhea, leukopenia
- 10% mortality
How is coronavirus transmitted?
- reservoir may be in animals
- transmitted by resp tract secretions via person to person contact or fomites
When do coronavirus infections occur?
- some sporatic
- outbreaks in winter/spring
What is MERS?
- middle east respiratory syndrome
- newly recognized pathogenic coronavirus
- no treatment currently
How is coronavirus diagnosed?
- PCR [respiratory, stool]
- antibody assays
- electron microscopy
What is treatment for coronavirus?
- supportive care
- steroids used to treat SARS-CoV associated respiratory distress syndrome [ARDS]
- no treatment for SARS
Where does transcription/translation occur in DNA viruses?
in nucleus
What is structure of adenovirus?
- linear
- double stranded
- DNA
- non-enveloped
- icosadeltahedron shape
How does adenovirus replicate?
- viral fibers attach glycoprotein member of Ig superfamily
- penton base interacts with integrin on host cell [helps endocytosis]
- DNA genome goes to nucleus
- transcription of mRNA in two phases
- capside proteins produced in cyto and transported to nucleus for viral assembly
- virus remains in cell and released when cell degenerated and lyses
short form: everything happens in the nucleus
What clinical syndromes associated with adenovirus
immunocompetent: pharyngitis + conjuctivitis [pink eye]
also: URI/LRI, gastroenteritis, cysitis
imunocompromised = more severe disease: pneumonia + respiratory failure, meningitis, encephalitis
How is adenovirus transmitted?
- by aerosol, close person-person contact, fecal-oral, fomites
- very contagious!
what is pathogenesis of adenovirus infection?
- virus establishes pharyngeal infection
- infects mucoepithelial cells in respiratory tract, GI, conjunctiva/cornea
- virus persists in lymphoid tissue
- viremia can occur if local replication
- then spreads to visceral organs
Where and when do adenovirus outbreaks occur?
in congregate settings –> military
no seasonality [all year round]
How is adenovirus diagnosed?
DFA
culture [for some serotypes]
PCR
How is adenovirus treated?
- usually supportive
- cidofovir for some immunocompromised
What is cidofovir? mech? type of administration? side effects?
- cytosine analog
- serves as substrate and inhibits viral DNA synthesis
- used to treat adenovirus in immunocompromised patients
- clear benefit has not been demonstrated
- IV administration
- side effect: nephrotoxic
What are clinical syndromes associated with rhinovirus?
- most frequent cause of common cold
- pharyngitis
- otitis media
- less commonly: bronchiolitis, pneumonia
what is the most frequent cause of common cold?
rhinovirus
How is rhinovirus transmitted?
aerool/droplets, fomites
hands are major vector!!
When do rhinovirus infections primarily occur? in which patients?
- in autum and late spring
- highest in infants and children
How is rhinovirus treated?
supportive
how can rhinovirus be prevented?
hand washing, disinfection contaminated objects
