Respiratory Viruses

Question 1

Orthomyxoviruses are the same as

Answer 1

Influenza Viruses

Question 2

Structure of orthomyxoviruses

Answer 2

Enveloped, (-) ssRNA, 8 separate nucleocapsids, helical

Question 3

Type A Orthomyxovirus

Answer 3

Antigenic shift and drift

Question 4

Type B Orthomyxovirus

Answer 4

Antigenic drift only, school-age, less antigenic

Question 5

Type C Orthomyxovirus

Answer 5

Stable, unlikely to cause disease

Question 6

Hemagglutinin (HA) protein

Answer 6

Attaches to sialic acid receptor on susceptible cell

Question 7

Neuraminidase (NA) protein

Answer 7

Enzyme the breaks down mucus which allows virus to attach via Hemagglutinin

Question 8

M2 Protein

Answer 8

Small membrane protein that is essential for entry of virus into susceptible cell

Question 9

Influenza Virus Entry

Answer 9

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

Question 10

Influenza Virus Replication

Answer 10

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

Question 11

Influenza Virus Budding

Answer 11

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

Question 12

Influenza A Pathogenesis

Answer 12

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

Question 13

Influenza Syndrome

Answer 13

Influenza syndrome – acute and self-limited, fever, congestion, sore throat and cough (cytokines)
Complications – primary viral pneumonia, secondary bacterial pneumonia, combined, myositis and heart involvement, Reyes syndrome (aspirin use), Guillain-Barre syndrome (ascending paralysis)

Question 14

Antigenic Drift

Answer 14

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

Question 15

Antigenic Shift

Answer 15

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

Question 16

Influenza A Outbreaks:

H5N1

Answer 16

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

Question 17

Influenza A Outbreaks: H1N1

Answer 17

H1N1 – swine origin, quadruple reassortment of human, swine and avian influenza

Question 18

Influenza Treatment:

Answer 18

Influenza Treatment:
Vaccines – H1N1, H3N2, Infl B - administered Oct/Nov before flue peak in Dec/Jan
Inactivated – Fluzone, Fluvirin, Fluarix
Live-attenuated – Flumist

Question 19

Amantadine/Rimantadine

Answer 19

• prevent opening of M2 ion channel prophylactically

Question 20

Neuraminidase inhibitors

Answer 20

– Zanamivir, Oseltamivir – prevents viral shedding

Question 21

Immunity

Answer 21

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

Question 22

Paramyxoviruses:

Answer 22

Paramyxoviruses:
Structure – enveloped, 1 (-) ssRNA, helical → cause giant cell syncytia
Attachment proteins – F + HN (Paramyxo, mumps), H (measles), G (RSV)
Replication – fusion entry → (-) strand → (+) strand, only in cytoplasm

Question 23

Measles:

Answer 23

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

Question 24

Mumps

Answer 24

Mumps: benign viral parotitis, T cell clearance

Sx – enlarged parotid gland (↑ amylase), could spread to pancreas, ovaries, testes, aseptic meningitis

Question 25

RSV: Respiratory Syncytial virus

Answer 25

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

Question 26

Human Metapneumovirus

Answer 26

Human Metapneumovirus – most everyone has Abs, clinically identical to RSV

Question 27

Parainfluenza virus

Answer 27

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

Question 28

Rubella

Answer 28

Rubella: Togaviridae, ss(+)RNA, icosahedral, enveloped

Sx – maculopapular rash (less red), prodrome (fever, rash, sore throat, lymphadenopathy, aka “3 day measles”

Question 29

Congenital Rubella syndrome

Answer 29

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

Question 30

MMR vaccine

Answer 30

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

Question 31

Common cold:

Answer 31

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

Question 32

SARS:

Answer 32

SARS: severe acute respiratory syndrome

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

Question 33

A two year-old boy is brought to the emergency room in February with coryza and a barking-like cough. Physical examination reveals a low-grade fever and an absence of wheezing and stridor. The patient is diagnosed to have the croup, given a single dose of dexamethasone to reduce the inflammation in the respiratory tract and sent home to rest. Which of the following viruses is most likely the cause of this child’s respiratory disease?

Answer 33

Answer: Parainfluenza virus

The barking cough is usually a symptom of the croup or laryngotracheitis. The croup is a common respiratory illness that is responsible for up to 15% of emergency department visits due to respiratory disease in children in the United States. The parainfluenza viruses are the major cause of the croup (50-75%) with parainfluenza virus type 1 being most common. A, B, C, and E are incorrect. The adenovirus a. , coronavirus b., bocavirus c. and rhinoviruses e. can also cause the croup but are not as common as the parainfluenza viruses.

Question 34

A 4-month-old boy is brought to the KUMC emergency department with rhinorrhea (nasal discharge) and tachypnea for the past 4 days. He had become lethargic, hypoxic and developed a fever during the night, which had prompted his mother to bring him to the ER. When interviewing the mother, the child had not been drinking or eating well for the past 1 to 2 days but had no vomiting or diarrhea. He had a cough and his mother reported that when he breathes, he sounds “funny.” The history reveals the child had been recently exposed to other sick children at his daycare center. A chest X-ray revealed an infiltrate in the middle right lobe and lung biopsy revealed cells that had formed “syncytia.” Tests for RSV and bacteria were negative. The child is hospitalized, put on supportive therapy and is released 4 days later. Which of the following viruses is most likely responsible for this child’s respiratory disease?

Answer 34

Answer:
Human metapneumovirus

Many viruses can cause respiratory disease in young children. The symptoms presented are indicative of RSV but tests for RSV are negative, in which case human metapneumovirus should be suspected. The paramyxoviruses are known for their ability to induce giant cell (syncytia) formation. None of the other four viruses are known to cause syncytia.