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3: Viral Genetics
SG 3
35
Veterinary Medicine
Professional
01/22/2016

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Term
Definition: Gene
Definition
-a nucleotide sequence that encodes for a specific polypeptide or protein
Term
The herpes virus genome contains about ___ genes.
Definition
-60
Term
What is mutation?
Definition
-changes in nucleotide sequence within viral genes
Term
What is substitution mutation?
Definition
-one (point mutation) or several nucleotide bases is/are substituted
Term
What is a deletion mutation?
Definition
-one or several nucleotie bases is/are deleted from the viral genome
Term
True or False: Mutations are always spontaneous.
Definition
-FALSE: may be spontaneous, induced, or engineered
Term
Do spontaneous mutations occur more quickly for DNA or RNA viruses?
Definition
-RNA
Term
In which three ways can induced mutations occur?
Definition
1) serial passage in hose animals or host cells (basis for some biral vaccines
2) exposing virus to UV rays and X rays (causes nicks and cross-linking of certain bases)
3) growing virus in presence of chemicals, anti-viral drugs, or at different temperatures
Term
What are a few possible consequences of mutations?
Definition
-adapt to an unnatural host
-increase or decrease in virulence: temp-sensetive mutants
-susceptibility of viruses to certain drugs can change: drug resistant mutants
-antigenic makeup changes: Ab escape/ resistant mutants
Term
Definition: Pseudotypes
Definition
-viruses that hace acquired the genotype of one parent and phenotype of another
Term
Definition: Mixed phenotype
Definition
-virus that cquired genotope of one parent and phenotype of both parents
Term
How does genetic recombination occur? How does this affect the nucleic acids of the resulting progeny?
Definition
-when two genetically different but related viruses infect the same cell and replicate, an exchange of nucleic acid between thhe parental viruses may occur
-thus progeny viruses can be formed whose nucleic acid is a combination of both parents
Term
Definition: Recombinants
Definition
-progeny viruses from genetic recombination whose nucleic acid is a combination of both parents
Term
How can recombinants be made in virto?
Definition
-inserting foreign DNA into a viral genome
Term
How does one make a rabies recombinant virus vaccine?
Definition
-ligate a rabies virus gene into the poxxvirus
Term
How do recombinant viruses come about naturally?
Definition
-when cellular genes are inserted in the viral genome during viral
replication in animals
Term
How can reassortment of influenza virus occur? In which type of animal are these primarily found in?
Definition
if a cell is infected iwth two different influenza viruses, progeny viruses can be produced hwhose genome consist of a mixture of segments derived from both viruses
-birds
Term
How do recombinant virus vaccines work?
Definition
-it is a virus vaccine that carries a foreign gene derved from another virus => ths foreign gene will encode for an immunogenic viral protein to which the vaccinated animal will mount an immu e resposne
Term
For a recombinant rabies vaccine, what is inserted into the other virus to cause an immun response?
Definition
-the gene that encodes for the G-glycoprotein of the rabies virus
Term
In addition to poxvirus, which other viruses hav been engineered to carry foreign genes into mammalian cells?
Definition
-papilloma virus
-adenovirus
-herpesvirus
-retrovirus
-parvovirus
Term
HOw is parvovirus usefulo to treat tumors?
Definition
-a gene to kill only the tumor cells is inserted into the parvovirus which is then given to the patient
Term
True or False: Because viruses are completely dependent on the metabolic pathways of the host cells for their replciation agents that interfere with viral replication are generally also toxic to cells and may seriously debilitate the patient.
Definition
-TRUE
Term
What are the three major proglems with chemotherapy?
Definition
=durgs can be toxic to cells and thus toxic to animals
-Antiviral drugs are mroe effective when given prophylactically
-resistance ot the antiviral durgs can occur fairly quickly with viruses (especially RNA viruses that can mutate at very high rates)
Term
What is the primary concern when developing an antiviral drug?
Definition
-that they kill only the virus, not normal cells
Term
HOw do receptor analog antiviral drugs work?
Definition
-they cause atachment of virion to cell receptor
Term
What are some of the many strategies for the development of antiviral drugs?
Definition
-attachment of virion to cell receptor
-block penetration and/or uncoating of viruses
-inhibit viral specific enzymes essential for replciation
-inhibit viral polymerases that transcrive the viral nucleic acid
-inhibit enzymes (proteases) needed for post-translational cleavage
-disrupts processing of RNA transcripts
-prevent translation of viral proteins - mRNA processing
-interfere with assembly of genetic material and capsid
Term
Describe the MOA of Idoxuridine and Trifluridine. What are they used to treat?
Definition
-converted into IdoxTP (an analop of TTP) and is inserted into the herpescirus DNA genome by DNA dep DNAP to block DNA replication
-used to treat herpesviurs but b/c it is very toxic it is only used as an ophthalmic drug to treat herpesvirus eye infections
Term
Describe the MOA of Adenine arabinoside. What is it used for?
Definition
-DNA dependant DNAP inserts VidTP (dATP analog) into the genima thus blocking DNA synth
-used topically in cases of herpesvirus infection
Term
describe the MOA of Acyclovir guanosine and Ganciclovir. What is it used to treat?
Definition
-after being transported into the cell by guanine transporter, it is phosphorylated by herpesvirus thymidine kinase (TK) into the active metabolite acyclovir tri-phosphate (only phosphorylated in herpesvirus infected cell)=> inhibits herpesviral DNAP thereby aborting the synthesis of viral DNA
Term
Describe the MOA of AMantadine. What is it used to treat?
Definition
-blocks the uncoating process of influenza virus by binding to the viral protein M2
-used to prevent and treat influanza virus A infection
Term
Describe the MOA of Azidothymidine. What is it used to treat?
Definition
-it is a pyrimidine nucleoside analogye that inhibits the action of reverse transcriptase (AZT-TP has 100X more affinity for HIV-RT than for mammalian DNAP)
-used against HIV, FeLV, and FIV
Term
What is Ribavirin used to treat? How does it work? Side effects?
Definition
-severe respiratory syncytial virus infection and for hepatitis C infection
-metabolised into nucleutodes resembing RNA nucleotides, inserted into the viral RNA, and are translated into non-functional viral proteins
-toxic and causes anemia with prolonged use
Term
What is Oseltamivir used to treat? How does it work?
Definition
-treatment and prophylaxis of Influenzavirus A and B
-it is an analogue neuramidase inhibitor preventing new viruses from emerging from infected cells
Term
What is historically special about Oseltamivir?
Definition
-was the first orally active neuraminidase inhibitor commercially developed
Term
How do protease inhibitors work?
Definition
-protease inhibitors block the late stages of viral replicative cycle and thus the post-translational cleavageof HIV polypeptides by proteases cannot occur
-treats HIV
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