21-22: Herpesviruses

Question 1

evolution and emergence of herpesviruses

Answer 1

pangaea - planet as it existed 250 million years ago
- moment when we think the first mammal appeared on earth, and also the first herpesvirus

extremely long co-evolution between mammals and herpesviruses
- lived with them for 250 million years

Question 2

herpesviruses as ubiquitous

Answer 2

many different hosts

all mammals infected with herpesviruses

Question 3

herpesviruses switching hosts

Answer 3

HSV2 crossing over but only 5 million years ago (rare event)

Question 4

advantages of herpesviruses

Answer 4

do not cause much disease
- don’t make the host very sick or die because you need transmission

extremely infectious
- so well evolved with the host
- whole point to infect a new host which drives evolution

infect a large fraction of the population

species-specific
- well-adapted since they co-evolved for such a long period of time that they only work well in that species

Question 5

structure of the virion

Answer 5

relatively large virus
- ebola has less than 10 genes but this one has over 70-80 genes

DNA genome

encodes 70-200+ proteins

Question 6

generalities about herpesviruses

Answer 6

successful pathogens, extremely well-adapted to hosts

no or little clinical symptoms
- true for healthy/immunocompetent people
- different for immunocomprised

high infection rates among host population
- most with 60%, some even up to 100%

life-long infection

Question 7

adoption of two different modes of life cycle for herpesviruses to persist

Answer 7

balance life cycle between two phases
- latency
- lytic

latency as a dormant phase
- virus enters, hides (in the nucleus) and has minimal impact
- completely silent and do not replicate

lytic with reactivation once in a while
- virus starts to make genes, takes over the cell, modifies it and turns it into a viral factory

always a low level of reactivation and creation of new viruses and new infections, so virus stays forever

Question 8

after primary infection, herpesviruses persist for life in their hosts in a latent stage

Answer 8

virus infects cells, releases nucleocapsids (shell protecting DNA genome)
- undetected by immune response since it is packaged by protein

viral DNA transported to the nucleus where it circularises
- circular form called an episome
- can remain like this for a long time with no/few genes expressed

infected cell is not aware if it is infected and will continue functioning normally

Question 9

latent stage can be interrupted by periods of lytic replication, termed reactivation

Answer 9

maintenance of viral reservoir in the host but once in a while, reactivation

lytic infection when episomes are replicated, reform linear DNA which is packaged into new virions that are released

reactivation as essential to allow viral spread to new hosts
- low level of spontaneous reactivation once in a while to replenish the reservoir within the host, or it would just die from natural causes

reactivation not associated with disease, but under certain circumstances, accompanied by clinical symptoms
- stimuli not well understood

Question 10

herpesviruses excel at evading both innate and adaptive immune response

Answer 10

typically, kiss of death from T cells which recognise infection, release factors to kill cells and go away
- very efficient mechanism for the body to get rid of infected cells

however, T cells released between 5-7 days after infection and if the virus has the ability to replicate/transmit to a new host in that time, it won’t be killed

when herpesviruses are latent, they are ignored by T cells
- with reactivation, many viral proteins/peptides so they can be displayed on the cell surface and targeted by T cells
- herpesviruses good at escaping recognition by T cells

viruses make viral proteins which interact with MHC-1 molecule surfaces, modifying them and targeting them for degradation