Respiratory Viruses I

Question 1

How are respiratory viruses transmitted, where do they interact with the host, and what is the initial result of infection?

Answer 1

• Virus reach respiratory tract by fomites, aerosol transmission
• Primary interaction between respiratory viruses and host occurs at epithelial surface
• Infection of epithelial cells results in release of cytokines which trigger many symptoms associated with viral infection (fever, aches, etc.)

Question 2

What changes between the upper and lower respiratory tracts and what consequence does this change have?

Answer 2

•Temperature differential between upper and lower respiratory tract. Consequences for pathogenesis
–Rhinoviruses replicate preferentially in URT. Note exception: Rhinovirus C (newly discovered, HRV-C is associated with pneumonia in adults and outbreaks of respiratory infections requiring hospitalization.
–Differential basis for attentuated viral vaccines (e.g. FluMist)

Question 3

What three patterns of respiratory viral replication are commonly seen?

Answer 3

• Acute Infection with replication confined to respiratory mucosal surface
• Persistent replication on respiratory mucosal surface
• Systemic replication after primary replication on respiratory mucosal surface

Question 4

What pattern of replication do the Paramyxovirus, Orthomyxovirus, Coronavirus, and Picornavirus display?

Answer 4

Acute infection with replication confined to respiratory mucosal surface

Question 5

What pattern of replication do the EBV, adenovirus, and papillomavirus display?

Answer 5

Persistent replication on respiratory mucosal surfaces

Question 6

What pattern of replication do the Paramyxovirus (mumps, measles), Varicella zoster, HHV6, CMV, Rubella, bunyaviruses, arenavirus, parvovirus, Picornavirus (poliovirus), poxviruses, reoviruses display?

Answer 6

Systemic replication after primary replication on respiratory mucosal surface

Question 7

What are the genera and representative species of the orthomyxoviridae?

Answer 7

Genus:
Influenzavirus

Species:
Influenza virus A, B, C

Question 8

What are the genera and representative species of the paramyxoviridae?

Answer 8

Three genera:
Paramyxovirus:
MUMPS, parainfluenzavirus 1-4, Newcastle disease

Morbillivirus:
MEASLES, rinderpest, canine distemper

Pneumovirus: Respiratory syncyticial virus

The handout also lists a fourth, even though it says three:
Henipavirus: Hendra and Nipah

Question 9

What is the genome and envelop status of the ortho and paramyxovirae?

Answer 9

Ortho:
Segmented (-) sense RNA
Enveloped

Para:
Non-segmented (-) sense RNA
Enveloped

Question 10

Where do the Orhto and Paramyxovirae replicate in infected cells?

Answer 10

Ortho: nucleus
Para: cytoplasm

Question 11

What are the surface marker proteins present on influenza viruses, and how many types of each are there?

Answer 11

Neuraminidase: 9 antigenic types (active enzyme)
Hemagglutinin: 13 antigenic types

•Variations in the HA and NA genes lead to designation of influenza sub-types (e.g. H1N1, H1N2 etc)

Question 12

How are influenza types classified into A, B, and C?

Answer 12

By the NP (nucleocapsid proteins) and M (matrix) proteins

Question 13

What differentiates Influenza A from B and C?

Answer 13

•Influenza A isolated from many animal species (birds, humans pigs and other species), B and C mainly human pathogens
•Surface glycoproteins of A have greater variability than B and C
•A and B are thought to be more closely related based on molecular similarities.
- Vaccines target A and B not C.

Question 14

Where does the influenza virus replicate and how long does the infection last? What are the consequences of each?

Answer 14

•Virus replicates in the ciliated epithelial cells of the U.R.T.
–Necrosis of these cells results in the usual symptoms of the acute respiratory infection (fever, chills, muscular aching. headache, prostration, anorexia).
•Normally self-limited infection usually lasts 3-7 days (+convalescence). Death from primary Influenza infection is very rare and appears to be determined by host factors rather than ‘virulence’ of virus.
–Damage to respiratory epithelium predisposes to secondary bacterial infections which accounts for most deaths today

Question 15

What diseases may result from an influenza infection?

Answer 15

Classic influenza syndrome (fever, chills, muscle aches, headache, prostration, anorexia)
Primary viral pneumonia
Secondary bacterial pneumonia

Central nervous system symptoms
Muscle involvement

Question 16

How does antigenic drift occur, what does it cause, and which types of influenza experience it?

Answer 16

Antigenic drift in HA and NA occurs by point mutations in gene, leading to an accumulation of amino acid sequence changes that alter the antigenic sites such that they are no longer recognized by host’s immune system. Found in Influenza A, B, and C.

Question 17

How does antigenic shift occur, what does it cause and which types of influenza experience it?

Answer 17

Antigenic shift is characterized by emergence of new major antigenic variants primarily in HA. These antigenic variants are genetic re-assortments that are generated when an H or an N gene from an influenza virus of some animal species is introduced into the gene set of an influenza virus pathogenic for humans.
•Antigenic shift occurs only in influenza A virus.

Question 18

How does genetic reassortment occur?

Answer 18

Single cells are infected by more than 1 virus, leading to reassortment of genetic segments because of segmented genome

Question 19

What two types of influenza vaccine are there, which flu types do they protect against, and how many valences do they have?

Answer 19

•The seasonal Flu vaccine is bi-valent and protects against circulating seasonal A and B Influenza viruses
•Two types of influenza vaccine
-Attenuated
-Killed virus vaccine

Question 20

What antiviral pharmaceuticals are available for influenza and what do they target?

Answer 20

– Neuraminidase inhibitors: zanamivir, oseltamivir, peramivir (investigational) for Influenza A and B
– Adamantane agents: amantadine and rimantadine for Influenza A.