Virology

Question 1

WHat are the two Virus theries?

Evidence for the RNA world theory?

Evidence for Reductionist theory?

Answer 1

RNA world theory
–Life arose with viruses

Reductionist theory
–Viruses came after cellular life; they are reduced versions of cellular organisms

RNA world evidence: Ribozyme- self replicating RNA

Reductionist evidence: Viruses have genes related to those of cellular genes, often pick up cellular genes

Question 2

What are ribozymes?

Answer 2

RNAs that can catalyze specific reactions (similar to enzymes)
-They can even catalyze their own synthesis

Question 3

Natural funcitons of ribsozymes?

3

Answer 3

1. cleave RNA,
2. viral replication,
3. tRNA biosynthesis

Question 4

DNA viruses start off how and end how?
3 Steps

Examples? 3

Answer 4

Start as DNA
then

Transcription to
RNA
then

Translation to
Protein

Ex: Herpes, Smallpox, Mimi

Question 5

RNA viruses start off how and end how?
2 Steps

Examples? 3

Answer 5

Start as RNA
then

Translation
to
Protein

Examples: Rhino, influenza, SARS

Question 6

Retroviruses start off how and end how?
4 Steps

Examples?1

Answer 6

Start as RNA
then

Reverse Transcription to
DNA
then

Transcription to RNA
then

Translation to
Protein

Examples: HIV

Question 7

DNA viral genome Pros?

3

Answer 7

1. Lower mutation rate
2. More stable (can carry more genes)
3. No dsRNA phase

Question 8

DNA viral genome cons?

2

Answer 8

1. Lower mutation rate

2. Slower replication

Question 9

RNA viral genome pros?

2

Answer 9

1. Fast replication rate

2. High mutation rate

Question 10

RNA viral genome cons?

3

Answer 10

1. High mutation rate
2. Limited sequence space (less stable)
3. dsRNA phase

Question 11

Why is HIV so highly mutated even in one single infected body?

Answer 11

They are a retrovirus which means they have a reverse transcriptase step that is different from the orderof the central dogma. This step is also where all the mutations are occurring (1 mutation per virus).

Question 12

What can’t HIV be cured by antiviral drugs?

Answer 12

It integrates into the cell (hides in it) so we cant get rid of it/recognize it

Question 13

Challenges in developing vaccines?

7

Answer 13

1. High mutation rate
2. Integration into the host genome
3. Infects immune privileged region of host
4. Targets immune system
5. Multiple serotypes
6. Costs and time involved in development
7. Vaccine safety concerns

Question 14

When do the earliest synmtpoms of HIV appear?

Answer 14

Earliest symptoms appear at two weeks (if at all)

Question 15

HIV mutation rate is what?

Answer 15

~1 base change per genome

25-30% in circulating HIV strains diveristy

Question 16

What are the most dangerous mutations in viruses?

2

Answer 16

• Some allow a competitive advantage

- Some allow escape from antiviral drugs

Question 17

Which retroviral proteins would you design drugs to target?

4

Answer 17

1. integrase,
2. reverse transcriptase
3. Protease inhibitors
4. Fusion entry inhibitors

Question 18

Describe the nucleotide analong mechanism?

Which drugs are these?
2

Answer 18

nucleoside analog mechanism (prevents adding onto the chain-chain terminator)
-because its so faster for the virus it mostly gets sucked by that instead of our own DNA

NRTI- purine and pyrimidine analogs

Question 19

3TC (Epivir/lamivudine) drug group?

MOA?

Answer 19

Reverse transcriptase inhibitor
-Nucleoside analog
(NRTI)

Cytidine mimic – acts as a chain terminator

Question 20

DLV (Rescriptor/delavirdine) drug group?

MOA?

Answer 20

Reverse transcriptase inhibitor (non-nucleoside)
NNRTI

Binds RT catalytic site, blocking polymerase function

Question 21

DRV (darunavir/Prezista) drug group?

MOA?
2

Answer 21

Protease inhibitor

1. binds the active site preventing the processing of viral protein precursors
2. Compete with the natural substrate

Question 22

EVG (Elvitegravir) drug group?

MOA?

Answer 22

Allosteric integrase inhibitor
INTI

Prevents functional multimers from forming (dimer of dimers = tetramer)

Question 23

MVC (Selzentry/maraviroc) drug group?

MOA?

Answer 23

Entry inhibitor/ CCR5 antagonist

Drug binds receptor (CCR5), preventing HIV from binding
Mutant binds receptor in a different conformation

Question 24

T20 (Fuzeon/entuvirtide) drug group?

MOA?

Answer 24

HIV fusion inhibitor

Mimics viral protein to displace it in the fusion complex– binds gp41 and prevents formation of the entry pore
(prevents the virus from fusing with healthy T cells)

Question 25

Immune-base HIV therapies? | 4

Answer 25

1. Therapeutic vaccines (DermaVir, Vacc-4x) 2. Gene therapy (Lexgenleucel-T, SB-728T) 3. Interleukin (IL-7, IL-2)-not indicated anymore 4. Chloroquine (Aralen, Plaquenil)

Question 26

SB-728T gene therapy MOA? What would the treatment process look like?

Answer 26

Modifies a CD4 T cell CCR5 receptor, making it non-functional Prevents HIV entry (only T cells affected and not all blood cells) Harvest patient T-cells, make the mutation and replicate, put back into patient

Question 27

What can be done to prevent escape mutants?

Answer 27

Multi-drug regime

Question 28

Potential effects of viruses on human evolution | 4

Answer 28

1. Immune system diversity 2. ABO blood system (decreased A allele frequency after smallpox epidemic) 3. Endogenous retroviruses (1% of genome) 4. Cell surface mutations (ex. CCR5)

Question 29

In humans, ERVs (endogenous retroviruses) have been associated with: 5

Answer 29

``` Multiple sclerosis Schizophrenia Cancer Autoimmune diseases Amyotrophic lateral sclerosis (ALS) ```

Question 30

Why do viruses start epidemics and then pandemics? | 4

Answer 30

1. Increased virulence (severity of disease or ability to spread) 2. Introduction into a novel setting 3. Changes in host susceptibility to the infectious agent 4. Changes in host exposure to the infectious agent

Question 31

Transmission modes for viruses? | 6

Answer 31

``` Iatrogenic Vertical transfer Droplet transmission Vector bourne Fecal oral route Sexual transmission ```

Question 32

What is a characteristic of zoonosis viruses?

Answer 32

Often diseases are adapted to their host and more deadly when they jump hosts (ex. Ebola)

Question 33

What kind of viruses are studied in BSL-4 Facilities? | 2

Answer 33

1. Aerosol viruses 2. Severe/fatal viruses with no vaccines or other treatments - Bolivian and Argentine hemorrhagic fevers - Marburg virus - Ebola virus - Lassa virus - Crimean-Congo hemorrhagic fever - Small pox

Question 34

Why is influenza so easily mutated?

Answer 34

influenza is a segmented genome so its great at recombination

Question 35

Why is quicker, earlier HIV treatment essential?

Answer 35

quicker treatment = less viral load for the rest of your life because of less infected cells