Lecture 3: Pathogenesis

Question 1

Define the two types of viral infections
-abortive vs. permissive

Answer 1

Abortive= virions not produced… why? B/c viruses cannot attach or enter the cell (if they enter, cannot replicate)
Permissive = infectious virions produced
-acute vs. persistent
(Chronic) (latent) (slow) (transforming)
Chronic- HIV
Latent- HSV, VZV
Slow- measles SSPE
Transforming- HPV
persistent viral infections: not completely cleared by the immune
acute viral infections: completely cleared

Question 2

What is an example of a permissive/persistent (chronic) viral infection ?

Answer 2

HIV
Continuous production and shedding of virions

Question 3

What is an example for a permissive/persistent (latent) viral infection?

Answer 3

HSV and (VZV) varicella
Virus is still present in the host
Periods of productive infection interspersed with long periods of no virion production

Question 4

What is an example for a permissive/persistent (slow) viral infection?

Answer 4

Measles, SSPE (subacute sclerosing pancephalities)
-SSPE: years after initial measles infection
Requires a slow accumulation of viral material

Question 5

What is an example for a permissive/persistent (transforming) viral infection?

Answer 5

HPV (human papilloma virus)
Results in uncontrolled cell growth (inactivates tumors suppressor proteins and impairs cell cycle regulation)

Question 6

What are some cytopathic effects?

Answer 6

These are visual changes in the host cells due to viral infection (may include cell death)
-histologies changes = inclusion bodies (in nucleus or cytoplasm)
-cell surface changes- syncytia

Question 7

What type of cytopathic effects involve in the formation of large multi-nucleated cells?

Answer 7

Syncytia
-fusion of infected cell with neighboring cells
-requires viral spike

Question 8

How do viruses cause cell damage that results in all that cytoplasmic effects?

Answer 8

1. By stopping normal cellular processes
2. By causing a loss of membrane integrity

Question 9

What are some ways viruses cause a loss of membrane integrity resulting in cytoplasmic effects?

Answer 9

-allowing an influx of ions (viral mRNA is maintained and can be translated while host mRNA is destroyed)
- insertion of viral glycoproteins in cell membrane (syncytia formation & immunocytopathic effects)

Question 10

What happens during Non-cytopathic effects?

Answer 10

1. Occur with viruses that do not kill the cell & still produce persistent infections
   -cells continues to grow and divide
2. Transformation infection (permissive) (persistent)

Question 11

Most common point of entry for viruses?

Answer 11

Mucosal surface
Respiratory tract most common point
-GI tract - naked viruses use this route as bile disrupts lipid envelopes
-Conjunctiva
-Urogenital tract

Question 12

What plays an important role in whether a permissive infection occurs?

Answer 12

Portal of entry (tropism)
Viruses cause different kinds of infections based on the tissue infected (varieties of staph infections depending on its portal of entry)

Question 13

What are the strategies to evade the immune system?

Answer 13

1. Overwhelm the host
2. Disarm innate immunity
3. Downregulate MHC molecules on cell surface
4. Interfere with NK cell activation/function
5. Hide
   No virus uses just one method of immune evasion

Question 14

What are immunologically privileged sites?

Answer 14

Eyes
Testes
Ovaries
Brain
-immune mechanisms are reduced in these location

Question 15

Local spread of a viral infection

Answer 15

Replication in the epithelial cells at, or near, the site of entry.
Syncytia
Common cold, influenza, rotavirus

Question 16

Generalized infection of a viral spread

Answer 16

From epithelial cells to subepithelial
Enter a lymph node, or blood stream (viremia)
Rapid vehicle for spread to a new niche

Question 17

Potential secondary viremia

Answer 17

Replication at remote sites
-specific issue beyond point of entry (hepatitis A)
-multiple tissues beyond point of entry= systemic infection (measles)

Question 18

Viral spread of HSV

Answer 18

Through peripheral nerves
-trigeminal nerve (site of viral latency)

Question 19

What are the viruses, bacteria, and parasites (TERATOGENS) that can cross the placenta and harm the fetus? VERTICAL TRANSMISSION

Answer 19

TORCH infections
T- toxoplasmosis (a parasite)
O- VZV, Zika, parvovirus B19, syphills, others
R- rubella
C - cytomegalovirus
H- herpes simplex virus

Question 20

When do clinical symptoms become apparent? What are some examples of immune responses?

Answer 20

-When enough cells are damaged or killed.
-edema (Swelling), inflammation (may be harmful (HCV) or helpful)

Question 21

Shedding
-localized vs. generalized

Answer 21

Release of new virions back into the environment
-shedding occurs from the same location = localized (influenza infects URT, sheds URT)
-shedding occurs from a location other than the infected site = generalized (poliovirus enters mouth, sheds through feces)
once shed, the virus can go to infect others

Question 22

When does shedding occur for localized infections

Answer 22

Shedding occurs from the same location as the infection site
(Influenza infects URT and virions are spread from the URT via coughing)

Question 23

When does shedding occur for generalized infections

Answer 23

Shedding occurs from a location other than the infection site
(Poliovirus enters through the mouth, but is shed through feces)
Once shed, the virus can go to infect others

Question 24

Infectiousness- the R0 value

Answer 24

How many new infections arise from a single infected individual
R0 of 2 = that each infected patient will infect 2 others on average
R0 of 18 = each infected patient will infect 18 others on average
how many people can one person infect

Question 25

R0 value can be used for

Answer 25

Can be used to calculate the % of the population that needs to be immune to achieve herd immunity
100*(1-1R0)

Question 26

% required of population needs to be immune for herd immunity for SARS-CoV with R0=3
Use formula

Answer 26

100(1-1/R0)
100(1-1/3)
=67% of the population needs to be immune for herd immunity