L4 - VIRUS-HOST

Question 1

Initial routes of virus infection

Answer 1

(primary viremia – does not dictate where the virus is going to end up or where it is going to be shed from)
* respiratory tract (e.g. influenza, COVID)
* oral cavity (e.g. hep A)
* genital tract (e.g. some herpesviruses, HIV)
* skin (e.g. rabies – but site of release is salivary gland, yellow fever)

Question 2

Viral spread and pathogenesis

Answer 2

• some viruses have a localized spread (target organ is the same as the portal of entry) - they replicate and are shed at the site of primary viremia and does not penetrate in the body through the bloodstream
  o ex. influenza, colds and many alimentary tract infections
• some viruses migrate through the body via circulatory and lymphatic systems to the target organ which is their major site of replication (secondary viremia), causing dissemination as opposed to localised infection.
  o Ex. smallpox: respiratory mucosa, spleen, bone marrow, lymph nodes
  o Ex. Measles: lymphatic and respiratory systems, skin, brain
• Further dissemination can occur to transport virus to site of shedding/ release
• the nervous system can also disseminate viruses by similar mechanisms (ex. rabies and herpesviruses)
  o migration through nerve cells could be problematic because nerve cells are very long, so it can take a long time to migrate through – during that time, virus can be attacked by antiviral defense mechanisms
  o Therefore, viruses must hijack the nerve cell’s transport system to travel quickly through the nerve cells

Question 3

Dissemination in plants

Answer 3

• Animal viruses can travel along mucosa for short distance spread
• But plant viruses can’t pass the plant cell wall for short distance spread from cell-cell
• Plant viruses use a movement protein which combines with viral +RNA to move it into new plant cells through plasmodesmata (communication channel between cells)

Question 4

Viral persistence (persistent infection)

Answer 4

• When virus is not cleared from the body
• often found by viruses infecting the immune, nervous, or digestive system
• involves modulation of both virus cell and host immune response

Question 5

• Viruses escape the immune system by:

Answer 5

o avoidance of neutralising antibodies by spreading directly from cell to cell
o budding into cytoplasmic vacuoles
o genetic variation (quasispecies - every progeny variant will have a different genomic sequence to the parental virus due to mutations)
o inhibition of immune and nonspecific defences
o becoming latent and reactivated later on
 downregulation of viral genome to avoid recognition of infection by cells
 have a reservoir where it stays in the latent form ex. HIV in resting memory t-cell

Question 6

Episomal virus

Answer 6

virus replicating independently
of the host chromosome

Question 7

Ex of persistent viruses:

Answer 7

Epstein Barr Virus (EBV)
* maintained in immune system
* expresses proteins that maintain the viral EBV episomal DNA
* also expresses proteins that downregulate certain host proteins immune system

Herpes simplex virus
* maintained in the nervous system (in latent form in the ganglion which is a protected site. The immune system can’t see inside the ganglion because nerve cells have immune privilege – can’t kill even if infected
* cold sores are cleared and reappear many times

Question 8

General host defences against viral infection (non-specific defences)

Answer 8

• anatomic barriers (ex. skin)
• non-specific inhibitors
• fever
  o viruses have adapted to have the highest rate of replication at the body temperature
  o fever increases the body temperature to prevent viruses from replicating at their optimal temperature
• inflammation
• phagocytosis (more effective against bacteria)
  o internalization and digestion of virus – but can also harbour virus infections and thus serve as reservoirs or vehicles for virus dissemination

Question 9

General host defences against viral infection (induced defenses: interferons)

Answer 9

• Induce resistance to viral replication in all cells by inducing the production of antiviral defence proteins that target diff stages of viral replication (L3)
• Increase MHC class I expression and antigen presentation in all cells
  o Make t-cell more efficient & immune system better at recognizing infected cells
• Activate natural killer (NK) cells to kill virus-infected cells
  o T-cell mediated killing of infected cell is specific – it is driven by the virus and requires antigen presentation to recognize particular epitope of virus and kill it, so it takes a long time to arise which might be too late since viral replication cycle is quick
  o NK cell-mediated killing of infected cell is non-specific – it is activated rapidly by interferons but is not as efficient as t-cells. They work to keep viral titre low at a manageable level until t-cells are produced