lecture 7

Question 1

explain host cell properties that limit virus host range at attachment and entry OR during macromolecular synthesis?

Answer 1

A) absence of receptor or co-receptor–> some use common molecules (silica acid) OR some use cell type surface proteins (HIV–>CD4)

B) absence of host transcription factors required for expression of virus genes

Question 2

what can influence trophism (host range)?

Answer 2

allelic differences & virion attachment proteins

• succès or failure of molecular recognition

Question 3

what are reasons to why only a subset of tissues in an organism were susepctible to infection?

Answer 3

may resulted if the virus used a receptor that was expressed on cells in the susceptible tissues but not expressed in all cells

Question 4

what is attachment?

Answer 4

lock & key interaction between cell surface molecule & protein on surface of virion

Question 5

what is a susceptible cell?

Answer 5

functional receptor for a given virus — the cell may or may not be able to support viral replication

Question 6

what is a resistant cell?

Answer 6

has no receptor— it may or may not be competent to support viral replication

Question 7

what is a permissive cell?

Answer 7

has the capacity to replicate virus–may or may not be susceptible

Question 8

what is a susceptible AND permissive cell?

Answer 8

only cell that can take up a virus and replicate it

Question 9

example of susceptible and permissive: transgenic mice express the human poliovirus receprtor to support replication

Answer 9

are permissive for replication but not susceptible to the infection

Question 10

virion attachment for influenza A?

Answer 10

hemagglutinin (HA)

Question 11

describe a human gene variant that limits the replication of most HIV 1 and the virus replication step affected by this mutation?
what is the evolution that has occurred?

Answer 11

deletion in CCR5 gene—> lack the CCR5 coreceptor

• people homozygous are resistant to CCR5 HIV at attachment and entry

-virus has evolved to used CxCR4 as a coreceptor , so CCr5 mutations are susceptible

Question 12

what happens at assembly at host range of influenza?
what protease has influenza developed?

Answer 12

hemagglutnina (HA) has 2 polypeptides

-mature HA needs cleavage via host protease

-most strains of influenza develop to use protease expressed only in upper respiratory tract

Question 13

what do highly virulent influenza viruses contain?
what does it do?

Answer 13

insertion of basic AA at HA cleavage site

permits cleavage by expressed intracellular proteases

Question 14

what do primates encode that restrict retrovirus?
what are antiviral restriction factors?

Answer 14

block replication steps for virus

• interfere with uncoating
  -binding and damaging ssDNA viral
  -tieing new visions to cells to prevent spread

Question 15

what is antiviral restriction factor Trim 5a?

Answer 15

against HIV 1
allelic differences among foster
bind to capsids–> affects uncoating and assembly

Question 16

in non permissive cells….
how are DNA tumor viruses transformed?

Answer 16

cell division is induced but cells are not killed
– interfering with cell cycle progression, regulation

Question 17

what steps can antivirals target?
why is it hard to make antiviral drugs than drugs that target bacteria?

Answer 17

viral uncoating
nucleic acid synthesis
integrase inhbitor
assembly and release of viral particles

–virus and cells share metabolic pathways

Question 18

what is chemo aimed at viral DNA or RNA synthesis

Answer 18

nucleoside analogs

Question 19

what replication step of HIV is inhibited by AZT?
why is it called chain terminating drug?

Answer 19

inhibits RT—> is a nucleoside analog that resembles thymidine but contains N3 group instead of OH on the ribose ring

–3OH on ribose ring necessary for DNA synthesis

• if RT incorporates AZT into growing DNA chain–> addiontal dNTPS will not be added

Question 20

what happens when SV40 enter permissive and non permissive cell?

Answer 20

SV40 have made mechanism to activate cell progression (cancer phenotype) –> produces DNA precursor that viruses need to replication

–after entering permissive cell—> Sv40 stimulates cell division and uses cell machinery to replicate its own DNA, express mRNA , and synthesize proteins –> progeny assemble and cell death

–Sv40 still stimulates cell division but fails to assemble progeny and kill the cell—> cell division ensues and leads to tumor

Question 21

what is selective toxicity and therapeutic index?

Answer 21

selective: desirable trait of drugs where the drug is more toxic to agent that the drug is targeting instead of the host

index: quantifies the difference between the concentration that is toxic to the agent and that which is toxic to the host

Question 22

how do antiviral drugs select for resistance?

Answer 22

as virus replicates, accumulate mutations–> whichever is most fit will dominate

antiviral drugs apply selective pressure on viral populations –> those populations that have variants that are not susceptible, these will dominant the population

Question 23

how does influenza enter?
how does amantadine inhibit influenza at entry?

Answer 23

influenza enters via endocytic route & M2 proteins in its outer membrane act as a ion channel that sense pH drop –> which is needed for uncoating

– blocks m2 protein, so can’t sense pH drop

*most influenze is resistant now

Question 24

what does HA have high affinity for and what happens?
what allows for new cells to be infected?
how does tamiflu work on influenze release?

Answer 24

-HA has high affinity for sialic acid–> causes budding cells to be attached to producer cell and unable to affect fresh cells

–neuroaminidase (NA) cleaves HA/SA linkages

–innhbits neuraminidase (NA), so HA/SA stay linked

Question 25

what is a protease inhibitor? what does it do?

Answer 25

ritonavir --> inhibits polyprotein processing affect some host proteases, metabolic effect emerge after taking this for a long time ** not commonly used**

Question 26

why is acyclovir more toxic to herpes than to uninfected cells?

Answer 26

--converted to a toxic substrate for DNA pol in presence of thymidine kinase --host cells have thymidine kinase, but host enzyme does not recognize the P acyclovir so it remains inert

Question 27

how does acyclovir work?

Answer 27

---herpes TK phosphorylates acyclovir --> host kinases add 2 and 3 P ---acyclovir tri-P can be used as a NTP by host DNA poly---> chain terminations and apoptosis

Question 28

what is the mechanism of paxlovid?

Answer 28

protease inhibitor that targets SARS COV2 protease --formulated with small amount of drug developed to inhibit HIV 1 protease

Question 29

why have protease inhibitors been stopped being used? why is paxlovid less toxic than drugs of this class that target HIV1?

Answer 29

cross reactivity wit host protease that could inhibit hormone maturation from precursor proteins that are initially synthesis --> any cross reactivity with paxlovid would be limited due to short duration -formulated with ritonavir----which cross reacts with human drug metabolism pathways, helps increase half life and effectiveness

Question 30

What does lenacapvir target? How is its mechanism like a host antiviral restriction factor ?

Answer 30

Binds HIV capside protein and interferes with uncoating and assembly Acts like Trime 5a, which binds capsid and prevents uncoating (monkey trim 5a works but human is resistant) If administered 2 times a year can prevent virus replication

Question 31

Sally was infected with a plaque-forming virus. Her friend harvested serum from Sally’s blood and diluted the serum ten-fold, then serially made two additional ten-fold dilutions, starting with a portion of the first dilution. The friend then plated separate 1 ml aliquots of the third dilution onto each of ten plates of cells. After plaques were allowed to form, each of the 10 plates had an average of 5 plaques apiece.  Roughly what amount of virus is in Sally’s serum? Group of answer choices

Answer 31

5000 pfu per ml 103 dilution * 5 plaques