Influenza

Question 1

Influenza types

Answer 1

Type A: influenza, severe disease, epidemics and pandemics
Type B: influenza, disease is less severe compared to type A, sporadic and epidemics
Type C: rare, mild course, sporadic, no epidemics or pandemics
Type D: Pigs

Question 2

Influenza basics

Answer 2

Family: Orthomyxoviridae.
(-)ss segmented RNA genome. Enveloped.
Surface protein of Influenza A/B: Hemagglutinin, Neuraminidase, Ion channel M2

Question 3

Hemagglutinin (HA) function

Answer 3

Binds sialic acid and facilitates viral entry.

Question 4

Neuraminidase (NA) function

Answer 4

Destroys sialic acid and facilitates virus release.

Question 5

Ion channel M2

Answer 5

Uncoating of viral particles

Question 6

Targets for antiviral intervention (influenza)

Answer 6

NA, M2

Question 7

Antigenic drift vs shit

Answer 7

Drift: amino acid exchanges in HA and NA (destroy ab binding sites), responsible for seasonal epidemics

Shift: exchange of entire genome segments (when 2 viruses co-infect same cell, =reassortment, nove virus!), responsible for pandemics

Question 8

Annual influenza epidemics are due to:

Answer 8

Antigenic drift,

Adaption of HA to ab pressure

Question 9

Influenza (A) - zoonosis

Answer 9

Natural reservoir: water fowl (all HA and NA subtypes present).

A-viruses infect mammals and birds. (H1-3 circulate in humans)

A-like viruses found in bats.

Question 10

Avian influenza (bird flu) - types

Answer 10

LPAIV: low pathogenic

HPAIV: highly pathogenic (high case fatality rate, but no human-human transmission)

Question 11

Avian influenza - why no human-to-human transmission?

Answer 11

Avian influenza A viruses: bind to 2,3-linked sialic acid
Human viruses: bind to 2,6-linked sialic acid

Expression of 2,3-linked sialic acid confined to lower respiratory tract of humans > limits ability of HPAIV to spread between humans

Also: temperature dependence of viral polymerase

Question 12

Is HPAIV transmission possible?

Answer 12

Adaptation of HPAIV to efficient airborne transmission is possible. Five amino acid substitutions are sufficient but these changes are associated with reduced virulence

Question 13

New strategy for antiviral therapy

Answer 13

Viral targets change and viruses easily acquire resistance.

But: host cell targets are constant > no resistance.

Question 14

How can host cell factors of viral spread be found? Ex for Influenza A

Answer 14

RNAi screens.

Influenza A host cell factors: vATPases, COPI proteins, neucleocytoplasmic transport, splicing

Question 15

Advantages of targeting host cell factors?

Answer 15

Suppression of resistance development.

Potential broadband antiviral activity if several viruses depend on one factor.

Question 16

HA priming principle

Answer 16

Viral GP are synthesized as inactive precursor depending on cleavage by host cell protease to transit into active state.

Priming of influenza virus HA (HPAIV: by furin) is essential for infectivity.

Cleavage site determines pathogenicity.

Question 17

HA cleavage sites in avian influenza

Answer 17

Low pathogenic: monobasic
High pathogenic: multibasic

Human influenza: monobasic, nut no correlation to pathogenicity

Question 18

Priming of human influenza A

Answer 18

In vitro: by several secreted and membrane ass. proteases (TMPRSS2 and HAT)

TMPRSS2 activates HA in cell culture and is expressed in viral target cells in lung

Question 19

TMPRSS2 relevance

Answer 19

Potential target for antiviral intervention.
Primes influenza A, SARS-COV/-2, etc.
KO mice have no phenotype in absence of infection.
Inhibitors might have broad-band antiviral activity without causing substantial unwanted side effects.