Viral genetics and antivirals

Question 1

What RNA viruses are treatable with drugs?

Answer 1

Hep C, HIV, Influenza, Croup

Question 2

What DNA viruses are treatable with drugs?

Answer 2

HPV, adeno, Hep B, some herpes, smallpox

Question 3

What four unique features of viruses can be targeted by antivirals?

Answer 3

viral entry, viral uncoating, nucleic acid synthesis, virion assembly/exit

Question 4

What are issues with antivirals ( 3 major ones)

Answer 4

Specificity (only targeting one feature of one virus, easily becomes resistant), Cyotoxicity, duration (most are just reversible so need lifelong treatment)

Question 5

What are some mechanisms that might be used to prevent resistance to antivirals?

Answer 5

Get rid of immunosuppression (transplant patients), combination of drugs with different targets, target host function

Question 6

What antiviral is used to treat HSV-1, HSV-2, and VZV? How does it work?

Answer 6

Acyclovir (aka valtrex); nucleoside analog of guanosine (missing the cyclic portion)

Question 7

What types of anti-virals exist?

Answer 7

Nucleoside analogs, non-nucleoside analogs, protease inhibitors, entry inhibitors

Question 8

How is CMV treated in those who have CMV retinitis or are immunocompromised? How does it work? Why isn’t it used for everyone?

Answer 8

Ganciclovir (aka valcyte), nucleoside analog, highly toxic, mutagenic and teratogenic

Question 9

How are people with chronic Hep B treated?

Answer 9

A combination of HIV and HCV treatment: PEG-IFN, enecavir (baraclude) and viread

Question 10

What are baraclude and viread? How do they work? What are they used for?

Answer 10

Anti-virals; nucleoside analogs; Hep B, HIV

Question 11

What are “broad spectrum treatment” for DNA viruses? What are their problems?

Answer 11

Foscarnet (foscavir) and Cidovir (Vistide); both are toxic to the kidney and can only be given by IV

Question 12

How is influenza treated? How do these antivirals work?

Answer 12

Zanamivir (Relenza) and Oseltamivir (Tamiflu); sialic acid analogs

Question 13

How is Hep C treated?

Answer 13

PEG-IFN and Ribavarin

Question 14

What do drugs target to block HIV? What is the currently used drug?

Answer 14

Block entry, reverse transcriptase, integrase, and protease; currently use stribild

Question 15

What is stribild used for? What does it contain?

Answer 15

HIV treatment, two reverse transcriptase inhibitors, an integrase inhibitor, and cobicistate (prevents breakdown in liver)

Question 16

What are the “broad sprectrum” antivirals for RNA viruses? How do they work?

Answer 16

Ribavirin- nucleoside analog of guanosine

Question 17

What are some unique features about viral genomes?

Answer 17

100% efficient (all of genome is used to make protein), reading frame can overlap, ribosomes can frame shift (aka translational frame shift), makes one big polypeptide that is then cleaved by proteases

Question 18

Define complementation in terms of virus interactions- what do the progeny look like?

Answer 18

Each of viruses is missing something on own and can’t reproduce on own, but when come to the same cell they support each other and reproduce;progeny identical to parents

Question 19

Define phenotypic mixing in terms of virus interactions- what do the progeny look like?

Answer 19

exchange of capsid proteins so progeny can infect cells they don’t normally bind to (called pseudotype) ; only lasts a single generation and then looks like parents

Question 20

Define recombination in terms of virus interactions- what do progeny look like?

Answer 20

Genetic crossover at points of homology– progeny are different than either of the parents, permanent change

Question 21

What is viral interference? How does this happen?

Answer 21

Infection by one virus blocks the infection of another virus; blocking the receptors, competition for resources, stimulation of innate immunity

Question 22

What types of diseases does gene therapy target?

Answer 22

Diseases that result from a single gene defect- CF, hemophilia, liver-enzyme deficiency, retinal disorders, and cancers

Question 23

What is the general procedure for making the molecules used in gene therapy?

Answer 23

Remove the essential gene in virus, clone the therapeutic gene, grow the virus in the packaging cell (cell that has the essential gene), test in cells

Question 24

What are some problems with gene therapy?

Answer 24

Viruses don’t have a long enough life span (expression turned off quickly); doesn’t spread across the entire tumor; immune system may still recognize as foreign and kill before getting to target tissue; need a huge dose to have an impact

Question 25

What are the 8 mechanisms of viral transmission?

Answer 25

Respiratory (aerosols), fecal-oral, contact (including fomites), zoonoses, blood, sexual, maternal-neonatal, genetic

Question 26

Whether or not a person gets sick from a virus and how severe their symptoms are depends on…?

Answer 26

Nature of the exposure (route in which you’re exposed), dose, status of the person (age/immunocompetency), virus/host interactions (certain HLA)

Question 27

What is primary viremia? Is the patient symptomatic?

Answer 27

First point where virus can be detected in the blood; during incubation and patient might not be aware

Question 28

What is secondary viremia?

Answer 28

Virus infects the organs where it is shed; high level of virus is detectable

Question 29

What are the four different responses that arise from viral infection?

Answer 29

Autoimmunity (symptomatic with clearance), unnoticed/asymptomatic, fatal, persistent

Question 30

What are the five general patterns of infection?

Answer 30

Acute, transforming, persistent, latent, slow