Lesson 52 (viral replication and antivirals)

What is the burst size

number of viral particles released from host cell when it bursts

What is the eclipse period

time after the virus has penetrated the cell and progeny leaves cell

the eclipse period is unrelated to the

incubation time (time between infection of host until it shows clinical signs)

Viral replication is studies ____ using cell cultures (in suspension or monolayer) in what is known as the growth curve of viruses

in vitro

There is a differences between _______ cell lines (virus can infect but not complete the replication cycle) and ________ cell lines (virus can infect and complete the cycle)

There is a differences between _susceptible_ cell lines (virus can infect but not complete the replication cycle) and _premissive_ cell lines (virus can infect and complete the cycle)

How do you study and unculturable virus

construct infectious clone (inserting ciral genome into plasmid)

What can reporter genes do?

ex fluorescent marker, can be added to these infectious clones to facilitate their study

What is viral attachment (1)

receptors on viral envelope or capsid become connected to complementary receptors and coreceptors on a cell membrane expressed in susceptible cells

What is viral penetration (2)

entry via membrane fusion or via endocytosis (receptor mediated used by naked viruses)

What is viral uncoating (3)

viral capsid open and frees genome, partial or complete

What proteins may take viral genome to nucleus if it is a virus that replicated there

chaperons

What is transcription (4-8)

genome to mRNA

What is translation (4-8)

mRNA to protein

What is replication (4-8)

genome coping itself

What is the order of transcription translation and replication in viruses

can differ based on DNR vs RNA and (+) vs (-) viruses

Polymerase of DNA virus that replicates in nucleus

cellular DNA-dependent RNA polymerase to produce mRNA

Polymerase of DNA virus that replicates in cytoplasm

carry DNA-dependent RNA polymerase of their own

What is characteristics of translation of (+) RNA viruses

code for RNA-dependent RNA polymerase, most can bind directly to ribosome and start translating, some capped with poly A tails

What is characteristics of translation of (-) RNA viruses

must carry own polymerase enzyme in nucleocapsid (RNA dependent RNA polymerase)

What does retrostranscripase produce

RNA dependent DNA polymerase…..produces DNA from RNA template)

What is assembly (9)

structural proteins of simple viruses associate spontaneously form capsomer → self assemble to form capsid

What do helical structured viruses assemble to create

pearl necklace (cylindrical helix)

One end of the viral genome has a ______ that binds to a protein that enables the entireness to the procapsid

One end of the viral genome has a _packing sequence_ that binds to a protein that enables the entireness to the procapsid

What is release (10) for naked viruses

usually accumulate in nucleus or cytoplasm until they exit from cell by lysis

What is release (10) for envoloped viruses

budding or exocytosis

How does retrovirus replication occur (a type of RNA virus)

use their own retrotranscriptase enzyme with RNA-dependent DNA polymerase capability → produce RNA-DNA hybrid → then ds DNA → insert into host genome

What intermediate do retroviruses replicate through

DNA

Why are LTR (long term repeats) important in retrovirus

1) allows viral genome to integrate to host genome

2) acts as strong promoter

Transcription of viral RNA occurs from ______

integrated (proviral) DNA

What are antivirals

agent that interfere with viral replication and are toxic to the cells

Why are antivirals common to adverse side effects

they target mechanisms that viruses use (they use our cellular machinery) so we get hit with the cross fire

Do antivirals cure the viral infection

NO in most instances; they usually ease symptoms and shorten the length of the viral infection

What type of infection are antivirals best suited for

persistent infections because there is more opportunities to interfere with viral replication

Why are there not alot of antivirals used in vet med

cost and lack of efficacy and safety clinical trials

How are most viral infections treated in vet med

symptomatically (alleviate symptoms) and palliatively (treat but not with the intent of curing)

What are some other approaches for handling viral infections in vet med

preventative vaccination, biosecurity, depopulation

In what animals can antivirals not be used in?

FOOD ANIMALS***

What do purine and pyrimidine analogs do?

act as chain terminators and stop viral DNA polymerase from adding further nucleotides

Acyclovir

inhibitor of herpesvirus DNA polymerase; prodrug that requires another vial coded enzyme to get phosphorylated to its active state

In what cells does acyclovir work in

activation only occurs in infected cells, drug is non toxic for uninfected cells

Remdesivir metabolite GS-441524

FIP antiviral (corona in cats)

1) phosphorylation 2) incorporation into viral RNA 3) termination of replication

Remdesivir/GS-441524 side effects

stone formation of nitrogen, carbon, oxygen

What does a drug cocktail do?

target different viral steps at same time

What are the major groups of antivirals

nucleic acid chain terminators (& polymerase inhibitors), protease inhibitors, integrase inhibitors, neuraminidase inhibitors, attachment inhibitors (monoclonal antibodies)