Viral Pathogens - Cashdollar

Question 1

1. Infections of what parts of the respiratory system are considered “upper respiratory infections”?
2. Lower respiratory infections?

Answer 1

Following list is in order from proximal to distal

• Upper
  
  • Sinusitis
  • Common cold
  • Pharyngitis
  • Epiglottitis
  • Laryngotracheitis
• Lower
  
  • Bronchitis
  • Bronchiolitis
  • Pneumonia

Question 2

Many respiratory viruses begin in the upper respiratory tract and some migrate to lower areas from there. Some viruses, however, can also spread into the blood, causing viremia and leading to systemic symptoms.

Name three types of respiratory viruses that are known to cause viremia.

Answer 2

1. Measles virus
2. Adenovirus
3. Enteroviruses

Question 3

Influenza Virus

• How many known subtypes of hemagglutinin (HA) are there?
• How many known subtypes of neuraminidase (NA) are there?

Answer 3

Influenza Virus

• 16 subtypes of HA
• 9 subtypes of NA

Question 4

Influenza Virus

Describe the difference between antigenic drift and antigenic shift

Answer 4

Influenza Virus

• Antigenic drift: Small changes in the “recognizability” (serologic relatendess) of the virus over several years. Mediated by point mutations.
• Antigenic shift: Large changes in serologic relatedness within a single year. Mediated by reassortment of HA and NA subtypes between two viral strains within a doubly-infected host.

Question 5

What are some important species of animal hosts of influenza?

Answer 5

• Aquatic Birds
• Pigs
• Poultry
• Cats
• Horses
• Dogs
• Aquatic Mammals

Question 6

Name three influenza strains that have historically been repsonsible for major pandemics

Answer 6

• H1N1 (Spanish flu, Russian flu, Swine flu)
• H2N2 (Asian flu)
• H3N2 (Hong Kong flu)

Question 7

What are two strains of avian influenza viruses that have been of recent concern regarding a possible pandemic in the future? Why are they a concern?

Answer 7

• ​H5N1
• H7N9

These two strains appear to cause severe symptoms and have a high mortality rate, although the limited data is skewed towards the severe cases, as they show up in hospitals.

Although these strains do not yet transmit easily between people, a future mutation could change allow for rapid transmission.

Question 8

Influenza

1. What cells does the influenza virus infect?
2. How does the virus cause cellular damage?
3. What is this celluar damage a risk for?
4. Is viremia a major concern?

Answer 8

Influenza

1. Ciliated epithelial cells lining the URT
2. Lytic viral replication and the cytotoxic T-cell response cause epithelial destruction
3. Epithelial destruction (both ciliated and mucus-secreting cells) disrupts the normal barrier and decreases clearance via the mucociliary escalator, increasing the risk of secondary bacterial infection
4. Viremia does not play a major role in pathogenesis

Question 9

If viremia is rare for influenza, how does it cause systemic symptoms beyond the respiratory tract?

Answer 9

The interferon and cytokine response to the virus cause the systemic symptoms.

Question 10

Name three bacterial infections that occur secondary to influenza infection.

Of what concern are these secondary infections?

Answer 10

1. Strep pneumo
2. Staph aureus
3. Haemophilus influenzae (HiB)

Secondary bacterial infections are the major cause of death in influenza

Question 11

Name four rare complications of influenza.

Answer 11

1. Myositis & cardiac involvement
2. Guillain-Barré syndrome
3. Encephalitis
4. Reye’s syndrome

Question 12

What two major forms of prevention and control of influenza infection? Name some specific examples

Answer 12

1. Vaccines
   
   • Formalin inactivated
   • Attenuated infectious virus
     
     • Intranasal
   • Quadrivalent
2. Antiviral drugs
   
   • Amantadine & Rimantadine
   • Zanamivir & Oseltamivir

Question 13

Describe the mechanisms of action of:

1. Amantadine & Rimantadine
2. Zanamivir & Oseltamivir

Which set of drugs is not currently often used?

Answer 13

1. A&R: Inhibit uncoating by blocking the M2 protein
   
   • Not used - high degree of antiviral resistance
2. Z&O: Neuraminidase inhibitors (inhibit release of progeny virus)

Question 14

Rhinovirus

1. What % of common colds are attributed to rhinovirus?
2. How many major subtypes are there? How many individual serotypes?
3. What other species act as a reservoir for rhinovirus?

Answer 14

Rhinovirus

1. 50%
2. 3 major, ~150 serotypes:
   
   • RV-A (75 serotypes)
   • RV-B (25)
   • RV-C (51)
3. Humans are the only natural host!

Question 15

Rhinovirus

1. How is rhinovirus transmitted?
2. What is the course of the infection like?
3. How can RV infection be prevented and controlled?

Answer 15

Rhinovirus

1. Respiratory secretions
   
   • Directly between individuals
   • Fomites
2. Mild, self-limiting infection
3. Prevention:
   
   • No antivirals or vaccines available
   • Handwashing
   • Disinfectants

Question 16

Enteroviruses

1. When do these viruses often cause common colds?
2. What preventative measures are available?

Answer 16

Enteroviruses

1. Responsible for Summer colds and flu
2. No vaccines or antivirals available - clean hands!

Question 17

1. Over just this past summer & fall, what specific strain of enterovirus has been of concern in the USA, including Wisconsin?
2. How does this virus spread?
3. Beyond mild to severe respiratory illness ,what are possible complications of this virus?

Answer 17

1. EV-D68
2. Respiratory secretions
3. Complications:
   
   • Flaccid paralysis
     
     • Several members of the EV family have been known to be a risk for paralytic disease in the past
   • Difficulty breathing & wheezing

Question 18

Coronaviruses

1. What % of common colds are attributed to coronaviruses?
2. What part of the respiratory tract is infected?
3. What preventative measures are there?

Answer 18

Coronaviruses

1. 10-15% (second most common cause)
2. Limited to upper RT
   
   • Exception has been seen with severe cases of MERS-CoV - Lower RT affected
3. No vaccines or antivirals available - containment measures (containment of animal reservoirs, hygiene, etc.)

Question 19

What two types of coronavirus have been responsible for serious illnesses over the past decade? What important animal reservoirs are there for these viruses?

Answer 19

1. SARS outbreak: SARS-CoV
   
   • Animal: bats
2. Acute pneumonia & renal failure: MERS-CoV
   
   • Animals: bats & camels

N.B. Currently, MERS-CoV does not appear to readily transmit from person to person. A mutation resulting in a more transmissable strain is a major concern.

Question 20

Parainfluenza Viruses

1. When do infections typically occur?
2. What is a major concern in infants and young children?
3. Is a vaccine available?

Answer 20

Parainfluenza Viruses

1. Fall & Winter
2. Croup (subglottal swelling may close airway)
3. No vaccine

Question 21

Parainfluenza Viruses

Describe the diseases caused by Types 1-4 of parainfluenza virus.

Answer 21

Parainfluenza Viruses

• Types 1 & 2: Common cause of croup
• Type 3: Similar to RSV, as it causes bronchiolitis in infants
• Type 4: Usually mild disease

Question 22

1. What is croup?
2. Describe the typical presentation of croup.

Answer 22

1. Croup: aka laryngotracheobronchitis. Inflammation around the larynx & vocal cords. Can cause respiratory distress.
2. Presentation:
   
   • Poor appetite
   • Sore throat
   • Fever
   • Hoarse voice
   • Barking seal cough
   • Stridor (high-pitched noise with inspiration)
   • Respiratory distress symptoms
     
     • e.g. nasal flaring

Question 23

Respiratory Syncytial Virus

1. How does it get its name?
2. How prevalent is it?
3. When and where are outbreaks seen?
4. Are reinfections common?
5. Is there a vaccine? Antivirals?

Answer 23

Respiratory Syncytial Virus

1. Virus causes fusion of infected cells into multinucleated syncytia
2. Infects virtually everyone by age 2
3. Outbreak during winter months in temperate climates (assumably from close quarters/indoors)
4. No - infections possible throughout life. Can be severe in the elderly
5. No vaccine, but antivirals helpful in cases where required

Question 24

RSV

How does an active RSV infection present in each of the following age groups?

1. Children < 1 yr
2. Children
3. “Older children” & adults

Answer 24

RSV

1. <1 yr: Bronchiolitis, pneumonia, or both
2. Children: Febrile rhinitis & pharyngitis
3. Older Child / Adult: Common cold

(Milder with age)

Question 25

**RSV** How is symptomatic RSV infection treated in each of the following cases? 1. Otherwise healthy infant 2. Premature infant 3. Immunocompromised infant

Answer 25

1. Healthy: * Supportive treatment * O₂ * IV fluids * nebulized cold steam 2. Premature: * Aerosolized **ribavirin** * Passive immunization with **anti-RSV Ig** & **human mAbs** 3. Immunocompromised: * Aerosolized **ribavirin** * anti-RSV Ig / mAbs will **not** work - deficient immune system cannot use the Abs

Question 26

**Metapneumovirus** 1. How does it present? 2. In what populations is severe disease seen? 3. How is it diagnosed? 4. How prevalent is it? 5. Are vaccines or antivirals available?

Answer 26

**Metapneumovirus** 1. Similar to RSV but milder 2. Infants, elderly, & immunocompromised 3. Use **RT-PCR** to definitely diagnose 4. Almost all children seropositive by age 5 5. **No** vaccine, **no** antivirals

Question 27

**Hendra and Nipah Viruses** 1. Why are these two emerging respiratory viruses a concern? 2. Where have human cases occured? 3. What are the important animal sources?

Answer 27

**Hendra and Nipah Viruses** 1. High mortality rates! 2. Australia & Asia 3. **Bats** originally, **Pigs** as intermediate

Question 28

**Adenovirus** 1. What types of disease does it cause? 2. What three adenoviruses have been associated with particularly severe respiratory symptoms? 3. What is seen in these cases?

Answer 28

**Adenovirus** 1. Wide spectrum of diseases (single virus does not usually cause all diseases - they have varying tissue tropism): * Respiratory infection * Conjunctivitis * GI infections * Hemorrhagic cystitis 2. Severe types: Adenoviruses **4, 7, and 14** 3. **Acute** & sometimes serious respiratory disease. Pneumonia in severe cases.

Question 29

**Adenovirus** * What types of respiratory infection are caused by adenoviruses in reference to viral life cycle? * When is systemic disease seen?

Answer 29

**Adenovirus** Can cause: * Acute * Persistent (w/ viral shedding) * Latent Systemic disease in the **immunocompromised**

Question 30

**Adenovirus** 1. Is a vaccine available? 2. Antiviral therapy?

Answer 30

**Adenovirus** 1. Live attenuated vaccine available for **military recruits** * None available for general public 2. **Cidofovir** can be used to treat severe infections in the immunocompromised

Question 31

**Measles** ## Footnote Name and describe the presentation of the four groups of clinical consequences due to measles virus infection.

Answer 31

**Measles** 1. **Measles** * **Characteristic Maculopapular rash** * **_C_**ough, **_C_**onjunctivites, **_C_**oryza (inflammation of nose mucus membrane) 2. **Atypical Measles** * More intense rash (esp. distal areas of body) * Possible vesicles, petechiae, purpura, urticaria (hives) 3. **Postmeasles Encephalitis** * Headache, confusion, vomiting, possible coma * **After rash dissipates** 4. **Subacute Sclerosing Panencephalitis** * CNS sxs * Personality, behavior, memory changes * Myoclonic jerks, spasticity * Blindness

Question 32

What is the most common cause of death in young children with measles?

Answer 32

Pneumonia

Question 33

What types of Herpesviruses are involved in human respiratory disease?

Answer 33

* EBV * HHV-6 * CMV * HSV

Question 34

Name two types of DNA viruses that cause human respiratory disease. Is their capsid enveloped or naked?

Answer 34

1. Adenoviridae - **naked** 2. Herpesviridae - **enveloped**

Question 35

What virus family contains: * rhinovirus * coxsackie virus * echovirus * enterovirus

Answer 35

**Picornaviridae**

Question 36

What virus family contains: * coronavirus * SARS-CoV * MERS-VoC

Answer 36

**Coronaviridae**

Question 37

What virus family contains: * Influenza A, B, and C viruses

Answer 37

**Orthomyxoviridae**

Question 38

What virus family contains: * Parainfluenza virus * RSV * Metapneumovirus * Measles virus

Answer 38

**Paramyxoviridae**

Question 39

(Note: this is simplified from the actual classification scheme to represent what was written in lecture.) Within the family **paramyxoviridae**, there are several **genera**. Name the four genera that contain each of the following four groups of viral species. 1. Contains measles virus 2. Contains parainfluenza viruses (1-4) & mumps virus 3. Contains RSV & metapneumovirus 4. Contains Hendra & Nipah viruses

Answer 39

The genera are: 1. Morbillivirus 2. Paramyxovirus * (Yes, it sounds just like the name of the viral family) 3. Pneumovirus 4. Henipavirus * (**Hen**dra + **Nipa**h = **Henipa**)

Question 40

Name 4 respiratory viruses within the **picornaviridae** family.

Answer 40

1. rhinovirus 2. coxsackie virus 3. echovirus 4. enterovirus

Question 41

Name the respiratory viruses within the coronaviridae family.

Answer 41

Coronaviruses, including: * SARS-CoV * MERS-CoV

Question 42

Name the respiratory viruses within the orthomyxoviridae family.

Answer 42

Influenza viruses A, B, and C

Question 43

Name 4 respiratory viruses within the paramyxoviridae family.

Answer 43

* Parainfluenza virus * RSV * Metapneumovirus * Measles virus