Respiratory Viruses

Question 1

Orthomyxoviruses:

Answer 1

aka Influenza viruses

Question 2

Orthomyxoviruses Structure

Answer 2

– enveloped, (-) ssRNA, 8 separate nucleocapsids, helical

Question 3

Type A

Answer 3

• Antigenic shift and drift

Question 4

Type B

Answer 4

• Antigenic drift only, school-age, less antigenic

Question 5

Type C

Answer 5

– stable, unlikely to cause disease

Question 6

Antigenic Drift

Answer 6

– accumualtion of point mutation of HA/NA that slightly changes the antigen, low in avian and high in human

Question 7

Antigenic Shift

Answer 7

– sudden major antigen change due to reassortment of 2 strains, recycling or gradual adaptation

Question 8

Glycoproteins

Answer 8

– NA, HA, M2 (Gp anchor), NS2, matrix protein, transcriptase complex

Question 9

HA

Answer 9

-trimeric hemagglutinin, 5 antigenic sites HA0 made in RER → Golgi to make HA1 and HA2 with a fusion peptide

Question 10

NA

Answer 10

– tetrameric neuraminidase, 2 antigenic sites, viral release

Question 11

NP

Answer 11

– holds segmented RNA together

Question 12

Influenza A:

Entry

Answer 12

– 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

Question 13

Influenza A: Replication

Answer 13

– nucleus/cytoplasm, forms (+) strands to translate into proteins and replication of more (-) strands for progeny

Question 14

Influenza A: Budding

Answer 14

– synthesized membrane GPs insert into cell membrane, packaged (-) strands bud out taking part of cell membrane

Question 15

Influenza A: Pathogenesis

Answer 15

– aerosol inoculation → replication in resp tract → killing of ciliated and mucus cells → activation of T cells, interferons and Ab → influenza syndrome and future protection

Question 16

Influenza syndrome

Answer 16

– acute and self-limited, fever, congestion, sore throat and cough (cytokines)

Question 17

Influenza syndrome Complications

Answer 17

– primary viral pneumonia, secondary bacterial pneumonia, combined, myositis and heart involvement, Reyes syndrome (aspirin use), Guillain-Barre syndrome (ascending paralysis)

Question 18

Influenza syndrome Pathogenicity

Answer 18

– string of basic residues at Arg cleavage site on HA0, cleavage by furin enzyme

Question 19

Influenza A Outbreaks:

H5N1

Answer 19

– 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

Question 20

H1N1

Answer 20

– swine origin, quadruple reassortment of human, swine and avian influenza

Question 21

Influenza Treatment:

Vaccines

Answer 21

H1N1, H3N2, Infl B - administered Oct/Nov before flue peak in Dec/Jan

Question 22

Influenza Treatment:
Vaccines
Inactivated

Answer 22

– Fluzone, Fluvirin, Fluarix

Question 23

Influenza Treatment:
Vaccines
Live-attenuated

Answer 23

– Flumist

Question 24

Influenza Treatment:

Amantadine/Rimantadine - prevent opening of M2 ion channel prophylactically

Answer 24

• prevent opening of M2 ion channel prophylactically

Question 25

Influenza Treatment: | Neuraminidase inhibitors

Answer 25

Neuraminidase inhibitors – Zanamivir, Oseltamivir – prevents viral shedding

Question 26

Influenza Treatment: Immunity

Answer 26

– long lived but subtype specific, secretory IgA is primary mediator for URT, T cells help clear virus

Question 27

Paramyxoviruses: | Structure

Answer 27

– enveloped, 1 (-) ssRNA, helical → cause giant cell syncytia Attachment proteins – F + HN (Paramyxo, mumps), H (measles), G (RSV)

Question 28

Paramyxoviruses: Replication

Answer 28

– fusion entry → (-) strand → (+) strand, only in cytoplasm

Question 29

Measles:

Answer 29

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

Question 30

Mumps:

Answer 30

benign viral parotitis, T cell clearance | Sx – enlarged parotid gland (↑ amylase), could spread to pancreas, ovaries, testes, aseptic meningitis

Question 31

RSV:

Answer 31

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

Question 32

Human Metapneumovirus –

Answer 32

– most everyone has Abs, clinically identical to RSV

Question 33

Parainfluenza virus

Answer 33

– ss(-)RNA, enveloped, close relation to mumps | Sx – croup (steeple sign, stridor), bronchiolitis, pneumonia

Question 34

Rubella:

Answer 34

Togaviridae, ss(+)RNA, icosahedral, enveloped | Sx – maculopapular rash (less red), prodrome (fever, rash, sore throat, lymphadenopathy, aka “3 day measles”

Question 35

Congenital Rubella syndrome

Answer 35

– 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

Question 36

MMR vaccine

Answer 36

– measles, mumps, rubella live-attenuated strains → 1 year, booster before school, before pregnancy Contraindications – egg or neomycin allergy, pregnancy, immunosuppressed, moderate/severe acute illness

Question 37

Common cold: virus highly variable

Answer 37

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

Question 38

SARS: severe acute respiratory syndrome

Answer 38

Coronaviridae -began in China, typical symptoms with a LRT infection and pneumonia