Viral genetics and antivirals Flashcards
What RNA viruses are treatable with drugs?
Hep C, HIV, Influenza, Croup
What DNA viruses are treatable with drugs?
HPV, adeno, Hep B, some herpes, smallpox
What four unique features of viruses can be targeted by antivirals?
viral entry, viral uncoating, nucleic acid synthesis, virion assembly/exit
What are issues with antivirals ( 3 major ones)
Specificity (only targeting one feature of one virus, easily becomes resistant), Cyotoxicity, duration (most are just reversible so need lifelong treatment)
What are some mechanisms that might be used to prevent resistance to antivirals?
Get rid of immunosuppression (transplant patients), combination of drugs with different targets, target host function
What antiviral is used to treat HSV-1, HSV-2, and VZV? How does it work?
Acyclovir (aka valtrex); nucleoside analog of guanosine (missing the cyclic portion)
What types of anti-virals exist?
Nucleoside analogs, non-nucleoside analogs, protease inhibitors, entry inhibitors
How is CMV treated in those who have CMV retinitis or are immunocompromised? How does it work? Why isn’t it used for everyone?
Ganciclovir (aka valcyte), nucleoside analog, highly toxic, mutagenic and teratogenic
How are people with chronic Hep B treated?
A combination of HIV and HCV treatment: PEG-IFN, enecavir (baraclude) and viread
What are baraclude and viread? How do they work? What are they used for?
Anti-virals; nucleoside analogs; Hep B, HIV
What are “broad spectrum treatment” for DNA viruses? What are their problems?
Foscarnet (foscavir) and Cidovir (Vistide); both are toxic to the kidney and can only be given by IV
How is influenza treated? How do these antivirals work?
Zanamivir (Relenza) and Oseltamivir (Tamiflu); sialic acid analogs
How is Hep C treated?
PEG-IFN and Ribavarin
What do drugs target to block HIV? What is the currently used drug?
Block entry, reverse transcriptase, integrase, and protease; currently use stribild
What is stribild used for? What does it contain?
HIV treatment, two reverse transcriptase inhibitors, an integrase inhibitor, and cobicistate (prevents breakdown in liver)
What are the “broad sprectrum” antivirals for RNA viruses? How do they work?
Ribavirin- nucleoside analog of guanosine
What are some unique features about viral genomes?
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
Define complementation in terms of virus interactions- what do the progeny look like?
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
Define phenotypic mixing in terms of virus interactions- what do the progeny look like?
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
Define recombination in terms of virus interactions- what do progeny look like?
Genetic crossover at points of homology– progeny are different than either of the parents, permanent change
What is viral interference? How does this happen?
Infection by one virus blocks the infection of another virus; blocking the receptors, competition for resources, stimulation of innate immunity
What types of diseases does gene therapy target?
Diseases that result from a single gene defect- CF, hemophilia, liver-enzyme deficiency, retinal disorders, and cancers
What is the general procedure for making the molecules used in gene therapy?
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
What are some problems with gene therapy?
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
What are the 8 mechanisms of viral transmission?
Respiratory (aerosols), fecal-oral, contact (including fomites), zoonoses, blood, sexual, maternal-neonatal, genetic
Whether or not a person gets sick from a virus and how severe their symptoms are depends on…?
Nature of the exposure (route in which you’re exposed), dose, status of the person (age/immunocompetency), virus/host interactions (certain HLA)
What is primary viremia? Is the patient symptomatic?
First point where virus can be detected in the blood; during incubation and patient might not be aware
What is secondary viremia?
Virus infects the organs where it is shed; high level of virus is detectable
What are the four different responses that arise from viral infection?
Autoimmunity (symptomatic with clearance), unnoticed/asymptomatic, fatal, persistent
What are the five general patterns of infection?
Acute, transforming, persistent, latent, slow
