Module 11: Viral Pathogenesis (Viral Evolution)

Question 1

Both host and viral genetics play a role in determining…

Answer 1

Viral virulence

Question 2

What are the types of changes a viral genome can undergo to alter viral virulence?

Answer 2

1) Mutation
2) Recombination
3) Reassortment

Question 3

While changes in the genome are needed for evolution and beneficial in the long term, a _______ genome is favored in the short term

Answer 3

A STABLE GENOME!

Question 4

How do organisms maintain a stable genome?

Answer 4

Bacteria, archaea, and eukarya maintain a stable genome by employing DNA repair and proofreading mechanisms to decrease mutation rate

Question 5

Why do viruses have higher mutation rates than bacteria, eukarya, and archaea?

Answer 5

Because viruses lack DNA repair and proofreading mechanisms!

Question 6

What viruses in particular have a very high mutation rate?

WHY?

Answer 6

RNA viruses have a very high mutation rate

BECAUSE –> They require the use of viral Rd-RP OR Rev. T which unlike RNApol, does NOT have a proofreading capability (cannot remove incorrectly added NTs)

Question 7

What is the mutation rate of RNA viruses?

Answer 7

10^-3 to 10^-5 bases per genome replication

(1 in 1,000 to 100,000)

Question 8

What are the 2 major implications of a higher mutation rate in viruses?

Answer 8

1) Production of heterogenous progeny populations

2) Rapid viral evolution

Question 9

How are heterogenous progeny populations produced?

Answer 9

Each time a virus replicates, a “viral swarm” forms due to the high mutation rate

–> Each divergent virus in the swarm is a quasispecies

Question 10

Viral Swarm

Answer 10

A population of related viruses that contain genomic mutations making the viruses genetically distinct

Question 11

Quasispecies

Answer 11

The divergent viruses within a viral swarm

Question 12

What are the implications of rapid viral evolution?

Answer 12

Makes it harder for us to fight and prevent viral infections

Question 13

What is the mutation rate of influenza?

Answer 13

10^-5

Question 14

Antigenic Drift

Answer 14

Gradual change in viral antigens due to random mutation (= mutational changes in viral surface proteins)

Question 15

How does antigenic drift impact Influenza and our ability to fight it?

Answer 15

Antigenic drift is strong in Influenza = HA + NA proteins are altered so significantly within just a few years to the point that our immune responses are ineffective against it

== Why there’s a new Flu vaccine each year

Question 16

HIV evolutions occurs…

Answer 16

WITHIN the host!

Question 17

What does HIV evolution within a host lead to?

Answer 17

1) Evolves ability to infect different cells

2) Evolves resistance to anti-retroviral therapies

Question 18

What are the 2 main types of HIV virions (in the cells they infect)?

Answer 18

1) Macrophage-tropic HIV

2) T-cell-tropic HIV

Question 19

Macrophage-tropic-HIV

Answer 19

Strain of HIV in which the gp120 protein binds to the CCR5 co-receptor on macrophages + monocytes

–> Most common form of HIV that is transmitted

Question 20

T-cell-tropic HIV

Answer 20

Strain of HIV in which the gp120 protein binds to the CXCR4 co-receptor on T-cells

–> Usually an evolved strain from original macrophage-tropic HIV

Question 21

What determines whether HIV infects T-cells or macrophages?

Answer 21

The structure of HIV gp120 surface protein and whether it binds to CCR5 or CXCR4 co-receptor

Question 22

Recombination

Answer 22

The process of combining 2 different/distinct pieces of nucleic acid

Question 23

Recombination of viral genomes can only happen when a host cell…

Answer 23

Is CO-INFECTED by genetically distinct strains of the SAME virus!

Question 24

Coronaviruses have what kind of genome?

Answer 24

(+) ssRNA

Question 25

What is unique about Coronavirus genome replication?

Answer 25

It is DISCONTINUOUS --> Involves "template switching"

Question 26

Template Switching

Answer 26

Process in which RNA polymerase begins RNA synthesis on one template strand but then DISSOCIATES and RNApol. along with the nascent RNA attach to: 1) a new location on the same template strand 2) a new template strand altogether ...and resume synthesis

Question 27

How do coronaviruses produce recombinant progeny?

Answer 27

Through template switching that occurs during genome replication of a co-infected host cell

Question 28

What is the genome of a recombinant viral progeny?

Answer 28

Have a recombinant genome consisting of sequences from two different viral inputs

Question 29

Viral Reassortment

Answer 29

-->The packaging of gene segments from 2 or more parental virus strains into ONE viral progeny A method of generating genetic variation ONLY within SEGMENTED viruses

Question 30

Segmented Virus

Answer 30

Virus with genome consisting of multiple distinct nucleic acid pieces (segments)

Question 31

How are viral reassortment and recombination SIMILAR?

Answer 31

BOTH can only occur in host cells co-infected by 2 or more distinct viral strains of the SAME virus

Question 32

How are viral reassortment and recombination DIFFERENT?

Answer 32

Recombination = Hybrid genome molecule forms Reassortment = NO hybrid genome molecule forms; just involves "mixing up" what segments become part of a viral progeny

Question 33

During viral reassortment, each progeny receives...

Answer 33

One copy of EACH segment = there is NO loss of segments

Question 34

Reassortment within influenza can produce progeny with...

Answer 34

HA and NA from two distinct viral strains!

Question 35

Reassorted Progeny may have genomes that contain:

Answer 35

1) Only segments from ONE of the viral "parents" 2) Segments from BOTH (or multiple) of the viral "parents"