Topic 16: Genetics of Virus
Genetics of Virus




Obligate intracellular parasites that depend on host cell for:
o Enzymes for metabolic processes such as DNA replication such as DNA polymerases
o Machinery for protein synthesis such as ribosomes
o Building blocks such as amino acids and nucleotides due to lack of means of
nutrition
o ATP as a form of energy due to inability to carry out cellular respiration
Can only reproduce within a living host cell
Termed as virions in extracellular states
o Metabolically inert, does not carry out respiratory/biosynthetic functions
o Structure by which the virus genome is carried from one cell to another
Viruses are infectious particles which are active as intracellular virus state, or inactive as
extracellular virion state, as opposed to living or non-living
Are viruses living or non-living?
Living:
 Viruses can reproduce
o They have genetic material (DNA/RNA)
o Encoding genes necessary for reproduction
o In intracellular states within compatible host cells
 Viruses can evolve with their host
o Viruses acquire genes from host cells
o Genetic recombination and horizontal gene transfers result in changing viral
genomes
 Viruses can react to environmental stimuli (such as radiation, chemicals and heat)
Non-Living:
 Able to exist in a metabolically inert state for extended periods of time
 Lack protoplasm and organelles
 Extracellular state: do not grow, obtain nutrition, respire, reproduce, synthesise proteins or
excrete
Basic Structure:
o Genome comprising or RNA or DNA
o Capsid comprising of protein subunits, capsomeres (protein coat)
o Envelope (in envelope viruses) comprising phospholipids from host cell
Viral Genome



Structure
Either DNA or RNA, but not both
Can be circular, linear, single-stranded or double-stranded
Contain genes for:
o Synthesising viral capsid and genetic material
Topic 16: Genetics of Virus


Envelope (only 
in envelope

viruses)

Capsid
o Regulating the action of host genes for packaging of mature virus
Surrounds the nucleic acid or encloses it
Constructed from identical protein subunits called capsomeres
Derived from host cell when virus is released by budding
Host cell’s surface membrane is incorporated i.e. phospholipid bilayer and
glycoproteins of viral origins
Protects the virion’s nucleic acid from the effects of various enzymes and
chemicals
Reproductive Cycle

Viruses can only replicate in suitable hose cells i.e. host range. This is obtained by a
complementary fit between viral surface glycoproteins and specific receptor molecules on
the surface of host cells
Comparison of Bacteriophages
T4
Lambda phage
Structure
 Long tail consisting of a tail
 Single tail fibre
sheath surrounding a central  Multiple tail fibres
tube to
 Multiple tail fibres
 Base plate
Genetic Material
Linear, double-stranded DNA
Location of capsid
Capsomeres surround the nucleic acid, contained in the head of the phage
Repro- 1.
 Multiple tail fibres attach to
 Single tail fibre attaches to specific
ductive Adsorption
specific receptor sites on the
receptor sites on the surface of
Cycle
surface of a bacterial host cell
bacterial host cell
 Base plate settles down on
 Base plate settles down on the host
the host cell surface
cell surface
2.
 Conformational changes occur in the tail sheath causing it to contract
Penetration  DNA is extruded from the head, through the tail (central) tube and
injected into the host cell passing through both the cell wall and cell
membrane
 Capsid is left on the outside of the bacterial cell wall
2A.
 Genome circularizes and inserts itself
prophage
into prophage insertion site on
formation
bacterial chromosome by genetic
recombination
 Integrated phage genome is known as a
prophage
 Viral DNA is replicated with host cell
DNA each time the cell divides, passing
on to generations of daughter cells
 Produces a large population of bacteria
carrying the virus in prophage form
Topic 16: Genetics of Virus
 With an environment trigger, the virus
switches from lysogenic cycle to lytic
cycle
 Lysis genes which were repressed
during lysogeny are activated,
allowing phage genome to exit from
bacterial chromosome to give rist to
new active phages
3. Synthesis  Synthesis of host DNA, RNA and proteins is halted
&
 Host cell machinery is taken over by the virus for nucleic acid synthesis
replication
 Host DNA is degraded into nucleotides, providing raw materials for
phage DNA replication
 Phage mRNAs are synthesised by host RNA polymerase via transcription
 Phage mRNAs are translated by host cell ribosomes, tRNAs and
translation factors into viral proteins and enzymes required to rake over
host cell and replicate phage nucleix acids
 These include enzymes for viral replication and inhibitory factors that
stop host cell RNA and protein synthesis
4. Assembly  3 separate sets of viral proteins are assembled to form phage heads,
tails and tail fibres each
 Different components are assembled into the complete bacteriophages
5. Release
 Phages lyse the host cell by the action of the enzyme lysozyme, which
digests the bacterial cell wall
 Water enters by osmosis, causing the cell to swell and burst
Comparison of Enveloped Animal Viruses
2B.
spontaneous
induction
Structure
Influenza Virus (orthomyxovirus)
 Nucleoprotein (NP) forms
nucleocapsid which associates
with nucleic acid
 Phospholipid bilayer envelope
 Surface glycoproteins
Hemagglutinin (HA) and
Neuraminidase (NA)
 Protein envelop: matrix protein
forms second layer of envelope,
enclosing nucleocapsid (M1monomer of matrix protein, M2acts as ion channel to lower or
maintain the pH of endosome)
 Enzymes
o PB1, PB2, PA form RNA
dependent RNA polymerase
responsible for replication and
transcription
o NS 1 regulates viral replication
mechanisms and cellular
signalling pathways
HIV (retrovirus)
 Capsid surrounding nucleic acid
 Phospholipid bilayer envelope
 Surface glycoproteins gp120 –
binds to CD4 receptors on white
blood cells like macrophages and T
helper cells, gp41 – aids in the
fusion of the HIV envelope and host
cell membrane
 Protein coat, matrix protein forms
second layer of protein envelop,
enclosing capsid
 Enzymes
o 2 Reverse transcriptase, each
associated with 1 RNA molecule
to reverse transcribe viral RNA
into DNA
o Integrase facilitates incorporation
of dsDNA into host cell’s genome
o Protease cleaves viral polypeptide
into functional proteins during
viral maturation
Topic 16: Genetics of Virus
Genetic Material
8 pieces of (-) sense single-stranded
RNA
Repro- 1.

ductive Adsorption
Cycle
2.

Penetration


3. Synthesis 
&
replication



2 identical molecules of singlestranded RNA + 2 reverse transcriptase
HA molecules on viral membrane 
bind to sialic acid containing
receptors on host cell membrane
Virus is taken in by receptormediated endocytosis, forming an
endocytic vesicle within an
endosome, with influenza virus
attached to its inner surface
Fusion of endosome with an acidic
lysosome lowers the pH of the
vesicle, triggering conformational
changes in the HA protein, causing
viral envelope and endosome
membranes to fuse, releasing the
8 viral segments into cytoplasm
Viral RNAs are then transported
into the nucleus
Viral replicase copies the (-) sense
RNA template into
complementary (+) sense RNA
The (+) sense RNAs are used as
templates for synthesis of fulllength (-) sense strand viral RNAs
by replicase
These (-) sense viral RNAs can be
packaged into new viral particles
as their nucleic acid
(+) sense RNAs are translated in
the cytoplasm by host protein
synthesis machinery to form
enzymes, matrix, capsomeres and
glycoproteins, which are
synthesized by RER-bound
ribosomes and are moved to Golgi
apparatus for glycosylation and
then incorporated into host cell
membrane via vesicle which fuse
with hose cell membrane









Glycoprotein gp120 binds to CD4, a
cell-surface receptor found on T
helper cells and macrophages of
host immune system
Upon binding to CD4, gp120
undergoes a conformational
change, allowing it to bind to a COreceptor, known as CXCR-4 on the
surface of T helper cells and CCR-5
on macrophages
HIV envelope fuses with the host
cell membrane, releasing the viral
contents consisting of viral nucleic
acid and enzymes into the host cell
Latency is achieved by integrating
into host’s genome
Reverse transcriptase first reverse
transcribes the viral RNA into a
complementary DNA strand
The RNA strand of the DNA-RNA is
broken down and the newly
synthesised DNA strand is used as a
template for synthesis of the other
complementary DNA strand,
forming a dsDNA molecule
This molecule then passes through
the nuclear pore and enters into the
host nucleus
Enzyme integrase catalyses the
integration of viral DNA into
genetic material of host, forming a
provirus
Latency ends when host cell is
stimulated in an immune response
Proviral DNA is transcribed by host
RNA polymerase into mRNA, which
is translated to produce long chains
of HIV proteins: matrix enzymes,
capsomeres and glycoproteins,
which are incorporated into host
cell membrane
Topic 16: Genetics of Virus
4. Assembly 

5. Release




Assembly of the viral particle is

complete when the viral
components of 8 (-) sense viral
RNAs associated with NP and
enzymes like PB1, PB2 and PA are 
packaged
Acquisition of the glycoprotein
stuffed membrane envelope
occurs during the release of the
virus

Virus is released by budding,

acquiring the host cell’s lipid
bilayer as virus envelope
Host membrane containing HA,

NA and M2 buds off from the
host cell with the virion
components.
With HA on viral envelope and
sialic-acid containing cellular
receptors, budding invariably
brings both together and results
in the new viral particle
remaining attached to host cell
NA then aids in release by
cleaving sialic-acid residues on
the cellular receptor that bind
the newly formed virions to the
cell
This releases the virions, allowing
infection to continue
Copies of HIV proteins and HIV’s
RNA genome assemble near the
host cell membrane to form a new
virus particle
Assembly of viral components
occur when 2 single-stranded RNA
molecules associated with reverse
transciptase and enzymes like
integrase and protease are
surrounded by assembled capsid
Acquisition of glycoprotein
studded membrane envelope
occurs during release of virus
The newly assembled immature
HIV buds off from the host cell,
surrounded by host membrane
HIV protease then cleaves the long
chains of HIV proteins into smaller
functional proteins, forming a
mature HIV particle
Pathogenesis
Spread by
Host cells
Infection
Influenza
Respiratory droplets
Epithelial cells of respiratory tract
 Adsorption and penetration of viral
genome into the host cell allows for
viral replication, which peaks
approximately 48 hours after
infection
 Production of virions deplete host
cells of essential raw materials like
HIV
Sexual or blood contact as virus travels
through the blood stream and adsorbs on
the surface of T helper cells
T helper cells
 Acute Phase: penetration of viral genome
into host cells allows for active replication
of new viral particles
 Immune response from host cell targets
and destroys infected T cells, causing
depletion of T cell population
 Chronic Phase (Clinical Latency Stage):
Topic 16: Genetics of Virus



Symptoms 



amino acids, ARP
Excessive budding of newly
synthesises virions deplete host cell
of cell membrane

Immune system of host recognises
viral glycoprotein on the infected
cells as “non-self” and white blood
cells attack and destroy infected
respiratory epithelial cells

Resultant depletion of epithelial cells
causes epithelial lining of the
respiratory tract to be lost

Excessive mucus production and 
swelling of the epithelial lining also
results due to irritation

Sore throat
High fever is response to subdue
infection
Shortness of breath due to swelling
and destruction of alveoli cells of
the lungs
Integration of viral DNA into host’s
genome, allowing T cells to evade
immune system, initiation the latent
phase of disease
Replication of inserted viral genome does
not happen unlike that of prophage as
terminally differentiated T helper cells do
not divide
Chronic Phase (Symptomatic phase):
upon stimulation of an immune response,
viral activation occurs and viral
replication actively occurs
Destruction of host cell’s white blood cell
population leads to an
immunocompromised state
Host is unable to initiate an immune
response against infections
Patients acquire AIDS, allowing for
opportunistic infections to occur as the
suppressed immune system is unable to
respond to any infection
Virus and Cancer
 Viral oncogenes trigger cancerous characteristics in cells
 Increase expression of proto-oncogenes
 Examples:
o Hepatitis B  liver cancer
o Human Papilloma viruses  cervix cancer
HPV





HPV-induced cancers often have viral sequences integrated into the cellular DNA, causing
latent infections and may also disrupt normal function of genes
HPV proteins such as E6 and E7 are known to act as oncogenes to promote tumour growth
E6 also binds to tumour suppressor protein, p53 to cause proteosomal degradation by
ubiquitins
Clearing by immune system only destroys actively dividing HPV viruses and does not affect
the integrated viral genomes
Process of transformation of normal cervical cells into cancerous ones are slow, cancer
only occurs in people who are infected with HPV for a long time