Respiratory Viruses Flashcards
Orthomyxoviruses:
aka Influenza viruses
Orthomyxoviruses Structure
– enveloped, (-) ssRNA, 8 separate nucleocapsids, helical
Type A
- Antigenic shift and drift
Type B
- Antigenic drift only, school-age, less antigenic
Type C
– stable, unlikely to cause disease
Antigenic Drift
– accumualtion of point mutation of HA/NA that slightly changes the antigen, low in avian and high in human
Antigenic Shift
– sudden major antigen change due to reassortment of 2 strains, recycling or gradual adaptation
Glycoproteins
– NA, HA, M2 (Gp anchor), NS2, matrix protein, transcriptase complex
HA
-trimeric hemagglutinin, 5 antigenic sites HA0 made in RER → Golgi to make HA1 and HA2 with a fusion peptide
NA
– tetrameric neuraminidase, 2 antigenic sites, viral release
NP
– holds segmented RNA together
Influenza A:
Entry
– sialic acid receptor → HA → endocytosis → fusion with acidic endosomes → M2 protein forms ion channel → HA conformational change → fusion of viral and cell membranes → release of genome
Influenza A: Replication
– nucleus/cytoplasm, forms (+) strands to translate into proteins and replication of more (-) strands for progeny
Influenza A: Budding
– synthesized membrane GPs insert into cell membrane, packaged (-) strands bud out taking part of cell membrane
Influenza A: Pathogenesis
– aerosol inoculation → replication in resp tract → killing of ciliated and mucus cells → activation of T cells, interferons and Ab → influenza syndrome and future protection
Influenza syndrome
– acute and self-limited, fever, congestion, sore throat and cough (cytokines)
Influenza syndrome Complications
– primary viral pneumonia, secondary bacterial pneumonia, combined, myositis and heart involvement, Reyes syndrome (aspirin use), Guillain-Barre syndrome (ascending paralysis)
Influenza syndrome Pathogenicity
– string of basic residues at Arg cleavage site on HA0, cleavage by furin enzyme
Influenza A Outbreaks:
H5N1
– high mortality rate, avian virus, no genetic reassortment
Receptor – sialic acid links via α2,3 instead of α2,6 → upper tract epithelia cells don’t bind, lower tract cells do bind
Cleavage site – highly basic residues, many tissues in the body will cleave, systemic spread
H1N1
– swine origin, quadruple reassortment of human, swine and avian influenza
Influenza Treatment:
Vaccines
H1N1, H3N2, Infl B - administered Oct/Nov before flue peak in Dec/Jan
Influenza Treatment:
Vaccines
Inactivated
– Fluzone, Fluvirin, Fluarix
Influenza Treatment:
Vaccines
Live-attenuated
– Flumist
Influenza Treatment:
Amantadine/Rimantadine - prevent opening of M2 ion channel prophylactically
- prevent opening of M2 ion channel prophylactically
Influenza Treatment:
Neuraminidase inhibitors
Neuraminidase inhibitors – Zanamivir, Oseltamivir – prevents viral shedding
Influenza Treatment: Immunity
– long lived but subtype specific, secretory IgA is primary mediator for URT, T cells help clear virus
Paramyxoviruses:
Structure
– enveloped, 1 (-) ssRNA, helical → cause giant cell syncytia
Attachment proteins – F + HN (Paramyxo, mumps), H (measles), G (RSV)
Paramyxoviruses: Replication
– fusion entry → (-) strand → (+) strand, only in cytoplasm
Measles:
infection of resp tract → lymphocytes and free virus in blood → conjunctiva, resp tract, GU tract, lymphatics, CNS, vessels
Sx – 101+ fever, CCC, maculopapular rash due to T cell response to infected endothelial cells, Koplik spots (white, mouth)
Complications – encephalitis, sclerosing panencephalitis, continued replication, malnutrition increases susceptibility
Mumps:
benign viral parotitis, T cell clearance
Sx – enlarged parotid gland (↑ amylase), could spread to pancreas, ovaries, testes, aseptic meningitis
RSV:
Respiratory Syncytial virus, high rate of hospitalization and infant death, most common cause of LRT disease in infants
Sx – bronchilitis, brochopnuemonia, and croup (hoarseness, barking cough) in infants, bronchitis is adults
Tx – ribavirin aerosol, -mabs directed to envelope GP of virus, oxygen therapy, no vaccine
Human Metapneumovirus –
– most everyone has Abs, clinically identical to RSV
Parainfluenza virus
– ss(-)RNA, enveloped, close relation to mumps
Sx – croup (steeple sign, stridor), bronchiolitis, pneumonia
Rubella:
Togaviridae, ss(+)RNA, icosahedral, enveloped
Sx – maculopapular rash (less red), prodrome (fever, rash, sore throat, lymphadenopathy, aka “3 day measles”
Congenital Rubella syndrome
– infection of fetus can lead to fetal death depending on gestational age
Triad – cataracts, sensorineural deafness, heart defects (patent ductus, pulm stenosis), first trimester is the worst
MMR vaccine
– measles, mumps, rubella live-attenuated strains → 1 year, booster before school, before pregnancy
Contraindications – egg or neomycin allergy, pregnancy, immunosuppressed, moderate/severe acute illness
Common cold: virus highly variable
Rhinovirus – picornavirus, naked, +ssRNA, acid-labile
Coronavirus - +ssRNA, enveloped
Transmission – hand contact, fomites, direct aerosol
Patho – virus replicates in URT epithelia → cell death → cell sloughing, lamina propria fluid
SARS: severe acute respiratory syndrome
Coronaviridae -began in China, typical symptoms with a LRT infection and pneumonia
