Virology Review Questions - Topic 1.
1. Lipid structures are not durable constructs (remember, there are no covalent bonds holding
adjacent lipid molecules together) and are highly susceptible to disruption such as
dehydration. The lipid layers often contain proteins that the virus uses as an anti-receptor
to bind to the host cell and the lipids themselves are often required for entry into the cell
via fusion of the viral envelope to the host cell membrane.
Non-enveloped viruses have a protein coat as their most exterior unit. Proteins are far less
susceptible to disruption than lipids and thus, these viruses are more hardy and likely to be
viable longer than envelope lipids.
2. The type of cell or cells that a specific virus is capable of infecting. The protein that the
virus uses as a virus receptor may be expressed in one species, or in several species. It may
be expressed on all cells, or only certain types of cells within an organism.
3. Host range is dependent on three factors: 1) the presence of the correct receptor on the host
cell’s surface (i.e., the virus receptor), 2) the presence of a complementary structure on the
virus that can bind to the host receptor (called the anti-receptor) and 3) the presence of
intracellular pathways and mechanisms that a virus is able to utilize for its replication.
4. The human cell is permissive but not susceptible. The virus cannot infect the cell through
the natural process, but if the attachment and entry step can be artificially bypassed, then
the human cell is capable of supporting the replication of the virus.
5. Blocking cellular surface structures that serve as viral receptors can impair cellular
functions, in some cases in a disastrous manner. It is important to remember that the virus
receptor has a completely different function to the cell it belongs to; it was never intended
to be used as a means for a virus to gain entry to the cell. Rather, over time, the virus
evolved to exploit that specific structure as a binding site. Also, the very same force that
drives a virus to evolve to a specific anti-receptor also often causes the virus to adapt to the
host cell’s “virus receptor” (a molecule that the cell uses for cellular functions and is
probably critical to the host cell). For example, HIV uses CD4 as its primary receptor. We
cannot block the CD4 molecule without disrupting immunological function – for example,
if it were blocked, the activation of T helper cells may be impaired.
6. Inactivated and subunit vaccines induce humoral immunity only. “Live” virus vaccines
had the potential of inducing cell mediated immunity in addition to humoral immunity –
the key point would be on whether it could infect and replicate in the vaccinated person.
Making vaccines is a lot like many wine – we all understand what has to happen, and how
it happens, but there is a bit of an “art” to the process as well. What we know is that one
type of vaccine works well for some viruses, but not for others. For example, the hepatitis
B vaccine is a subunit vaccine – the attenuated version is a bit too risky to use (it could
cause serious disease, and possibly oncogenic infections). The inactivated version of the
vaccine did not work well – it is possible that the treatment needed to render it inactive
(i.e., heat, chemicals) also damaged the virus’ epitopes, so that the antibodies that were
generated were not going to be sufficient to prevent the virus from binding to the host cell.
The subunit vaccine gets around both of these problems – the gene for the coat protein was 2
isolated and cloned into E. coli. The bacteria make the protein and secrete into the culture
medium and it is purified for use. When injected, the person gets the opportunity to make
antibodies that should neutralize the virus (if they get infected) but there is no risk of the
person getting hepatitis from the vaccination process.
What about the common cold and Ebola. The key difference is the lethality of the viruses.
Infection with the common cold virus is a mere annoyance when compared to infection
with Ebola. A common cold vaccine could be based on either an attenuated, inactive or
subunit vaccine, whereas an Ebola vaccine, if it existed, would probably be limited to an
inactivated vaccine or, more likely, a subunit method.
An attenuated vaccine is safer to administer with the common flu than Ebola since if the
common cold virus in the vaccine reverts to a pathogenic state, the effect on the recipient
would not be threatening. If an Ebola attenuated vaccine were to revert, the effects would
be deadly (people that are lethally infected bleed out from every body orifice.
Even an inactivated vaccine would pose a risk with Ebola as if a mistake was made during
its production and the virus was not inactivated, it would cause significant damage to the
recipient. This sounds unlikely, but one of the early batches of the inactivated polio
vaccine wasn’t properly inactivated, and several child suffered paralytic polio in the limb
that the vaccine was introduced. However, with today’s strict standards, a repeat of this is
A subunit vaccine would be best for Ebola as it possesses the lowest chance of potentially
causing disease in the recipient. For the common cold, an attenuated would be best as it
would promote the most effective immune response since it would mimic the natural
7. An antiviral drug would have to target virus specific activities – that may not be easy to do.
Remember, viruses are using the molecular machinery of the cell to replicate. A drug that
inhibits viral protein synthesis would also inhibit cellular protein synthesis – the drug
would affect healthy cells as well. The problems are compounded by the fact that many
viruses have RNA genomes, and are subject to mutation. A pharmaceutical company that
spends millions developing a drug for the common cold would find that within a year or so,
there are strains of virus that are resistant to the medication.
Virology Review Questions - Topic 2 - Picornavirus Case Sudy.
8. This class of virus is characterized by their strong resistance to the low pH conditions of
the gastrointestinal tract as well as resistance to various disinfectants such as the chlorine
used in swimming pools. This is in part due to the fact that they are a naked virus.
9. Poliovirus utilizes a polyprotein because its genome is composed of a single strand of (+)
RNA which encodes for all its proteins. However, the eukaryotic protein translation
system is unable to translate the individual genes of the poliovirus genome due to the
polycistronic nature of the viral RNA. The eukaryotic ribosome is not able to re-assemble
in the middle of an mRNA. As such, poliovirus creates a large polyprotein that has
autocatalytic abilities; it will cleave itself into smaller units. 3
10. The 5’ UTR is important in translation and possibly packaging. For translation, it forms
part of the IRES, a secondary structure in the RNA that can hydrogen bond with the rRNA
of the ribosomes. Without it, the ribosomes will not be able to assemble on the poliovirus
RNA so translation will not occur. No progeny will be produced as a result of the infection
and the infection will fail.
11. VPg is a protein-nucleic acid hybrid that provides an open 3’-OH group via the attached
nucleotides. It is used as a primer by the RNA dependent RNA polymerase during
poliovirus genome replication. Without VPg, poliovirus genome replication would not
occur as there would be no open 3’-OH group where the viral RNA polymerase could add
12. The poliovirus genome is replicated in replication compartments; large viral modified lipid
bound units that originate from the ER. Viral proteins are translated and then trafficked to
these compartments to carryout the replication and assembly of the virus progeny. The
advantage to the poliovirus is that it keeps the concentration of the reactants (in this case,
RNA, VPg and RDRP) in a high enough concentration to allow the reaction to proceed, it
protects the poliovirus RNA from cellular RNases, and it prevents the RDRP from acting
on eukaryotic mRNAs.
13. The poliovirus produces a protease (protein 2A) that modifies part of the cap binding
complex (CBC) that is part of the host cell mRNA. This CBC enables the eukaryotic
mRNA to interact with the ribosome, so that the ribosome can assemble. Since poliovirus
does not have a 5’ cap on its RNA and relies on a secondary structure in its RNA to
facilitate ribosome assembly (the IRES), this damage to the host cell’s mRNA CBC is an
advantage (for the virus) because it has reduces the competition for the ribosomes – the
host’s 5’ cap RNA can no longer bind to be translated. The host mRNA does not have a
“backup” mechanism, so the ribosomes are available to translate the poliovirus RNA.
14. In the replication cycle for poliovirus, the (–) RNA is used as template to create more (+)
(genomic) RNA to serve either as the genome for future viruses or to serve as mRNA for
further translation. It is important that the virus packages the (+) RNA as no RDRP is
packaged into the capsid (the internal cavity of the poliovirus capsid is so small, that the
only thing that there is space for is the RNA itself). It uses a recognition sequence on the
(+) RNA called the PAC site – this region of RNA interacts with the capsid (protein –
nucleic acid interactions are a common theme in biology).
15. 60 copies of VP0, 60 copies of VP1 and 60 copies are VP3 are needed to assemble the pro-
capsid (180 polypeptides total).
During maturation, each VP0 is cleaved to form VP2 and VP4 – this is done by the RNA
molecule itself. After maturation, there are 60 copies of VP1, VP2, VP3 and VP4 (240
16. IPV – Inactivated poliovirus vaccine which is delivered via an injection.
OPV – Oral poliovirus vaccine, an attenuated virus given in syrup form. 4
IPV triggers a humoral response the results in systemic immunity via poliovirus
neutralizing IgG in the blood. OPV elicits a humoral response that results in systemic IgG
as well as a localized IgA response in the gastrointestingal tract
IPV advantages – There is no risk of reversion and it promotes a strong, protective immune
response, can be used with the immune compromised people or infants that don’t have fully
developed immune systems
OPV advantages – It is believed immunity lasts longer than an IPV based one. Immunity
includes both systemic and localized antibodies
IPV disadvantage – It is expensive to make, maintain and administer. As well, it only
produces a systemic response and requires booster shots
OPV disadvantage – It has the potential for a reversion. It can also not be given to the
immune compromised people
Children in North America get an inactivated form of the vaccine. For children who are
traveling in endemic areas, it would be best to get an attenuated virus vaccine so they have
a stronger, longer lasting immunity that will protect them better. In addition, once they
have cleared the virus from the vaccine, they will make IgA antibodies in their gut
secretions. This child could no longer be a carrier of the virus, and cause infections in