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Midterm

Biology 1001A Study Guide - Midterm Guide: Dna Polymerase, Reverse Transcriptase, Drug Design


Department
Biology
Course Code
BIOL 1001A
Professor
Tom Haffie
Study Guide
Midterm

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1) Characteristics of viruses and why they are not generally considered to be “alive”.
- Not considered living because they lack many properties of life:
o They lack a metabolic system and cannot produce energy on their own
o They cannot reproduce on their own; must rely on a host cell.
- A virus is simply 1 or more nucleic acids surrounded by a capsid (protein coat).
- Most take 1 out of 2 structural shapes:
- Their structure is generally the smallest possible so they can transfer their genome from
one host cell to another.
- Does not have a cytoplasm enclosed by a cell membrane.
o Helical- Has protein subunits assembled in a rod-life spiral around genome.
o Polyhedral- Coat proteins form triangular units that fit similarly to a soccer ball.
Some have protein spikes that provide host cell recognition.
2) Why viral infections are usually difficult to treat with drugs, and exceptions to this
general principle
- Difficult to treat because for the most of the infection they are hidden inside host cells,
and use the host cell’s machinery to replicate. Drugs have no viral product to target.
- Antibiotics and other treatments typically have no effect on viral infections.
- The viruses maybe mutate enough or too quickly for a vaccine to be effective.
- Exceptions are Viruses with their own polymerases such as influenza provide a more
obvious target than ones hidden inside host cells.
3) Whether viruses are always pathogenic.
- NO
o Can be used as a vector for gene therapy
o When infected, non-pathogenic viruses may interfere a pathogenic virus’s ability
to replicate/function in a human host cell.
o Can be used as natural means to control pests.
o They are sometimes the dominant entity in some ecosystems (e.g. ocean), and
affect nutrient cycling.
4) Hypotheses for the evolutionary origin of viruses.
- Possibly could have been an escaped fragment of RNA/DNA from the genetic material of
a living cell (they came into existence after cells appeared);
o Since they can only duplicate via infection, cells must have been present before.
- A recent theory suggests that viruses are ancient; virus like particles predated the first
cells.
o The first viruses originated from a primordial gene pool (a pool of RNA
speculated to be the first genetic material).
- Note that there is no common evolutionary origin for viruses.

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5) Lifecycle of HIV.
a) HIV binds onto host’s plasma membrane using its protein receptors.
b) Viral contents enter cell via endocytosis.
c) R.T (reverse transcriptase) catalyzes and synthesizes a DNA copy of the viral RNA
strand, and then a 2nd DNA copy complementary to the first copy.
d) The double stranded DNA is integrated into host cell’s DNA
e) Transcription of DNA results in production of RNA. This RNA can serve as the
genome for new viruses and be translated to produce viral proteins.
f) Complete HIV particles are assembled and burst out:
a. In macrophages, it buds out without rupturing it
b. In T cells, it exits via rupturing the cell and which kills the cell.
c.
6) Characteristics of HIV that affect the prospects for drug design and vaccine
development.
- R.T. is a good target as it is a unique feature of HIV.
o However, R.T. is a huge reason why HIV mutates very quickly. When
synthesizing DNA, it does not have any proof reading capabilities, so errors made
persist.
- It can mutate very quickly and extensively, causing it to become highly resistant to many
vaccines.

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7) The general mechanisms by which vaccines protect against diseases.
- A dead or weakened virus is injected into the host; body learns how to recognize and
fight it.
8) Why developing a vaccine against HIV is relatively challenging, compared to other
diseases.
- Due to R.T., it can mutate very quickly and extensively, causing it to become highly
resistant to most vaccines. When synthesizing DNA, R.T. does not have any proof
reading capabilities, so errors made in the DNA persist. The proteins produced by the
mutated DNA could be different than the original virus
o For example, if the proteins on the viral coat changed then existing antibodies will
fail to recognize it.
9) Why people are encouraged to get a flu vaccine each year (as opposed to one time
only).
o The influenza virus mutates quickly, future generations can become immune to
old vaccines.
10) Major steps in lifecycle of HIV, and which of these are appropriate targets for
antiviral drug design
- Similar to 5) and 6). Lifecycle:
o HIV binds onto host’s plasma membrane using its protein receptors.
o Viral contents enter cell via endocytosis.
o R.T (reverse transcriptase) catalyzes and synthesizes a DNA copy of the viral
RNA strand, and then a 2nd DNA copy complementary to the first copy.
o The double stranded DNA is integrated into host cell’s DNA
o Transcription of DNA results in production of RNA. This RNA can serve as the
genome for new viruses and be translated to produce viral proteins.
o Complete HIV particles are assembled and burst out:
In macrophages, it buds out without rupturing it
In T cells, it exits via rupturing the cell and which kills the cell.
- Reverse Transcriptase is a good target since it is unique feature to HIV.
- 5 antiretroviral drugs which may help with treatment against HIV:
o Entry inhibitors,
o Non-nucleoside reverse transcriptase inhibitors,
o Nucleoside/Nucleotide reverse transcriptase inhibitors,
o Integrase inhibitors
o Protease inhibitor
11) Mechanism by which AZT interferes with HIV replication
- AZT mimics Thymidine (has similar shape) and fools R.T.
o As R.T. occurs, nucleotides are grabbed to make a new strand. If AZT is grabbed
and inserted into the strand, DNA synthesis stops.
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