Genetics and Inheritance (9744) Viruses 2017

 Are viruses are considered living or non-living? Living as they contain genetic material. However, non-living because they have no cellular organization and only show characteristics of living
things when in host cell.
Characteristics of living things include1) metabolic activity 2) cellular organization 3) ability to reproduce and grow in numbers 4) ability to respond to stimuli and adapt to environment
 Why are viruses obligate parasites? This is because viruses, like obligate parasites, depend on host cells to complete their life cycle.

Structure of Viruses
Bacteriophages Animal Viruses
Size: 10-300nm Enveloped
T4 Lambda Influenza Human Immunodeficiency Virus
phage phage (HIV)
Genome  Double-  (-) strand RNA  (+) strand RNA
 Nucleic acid that codes for synthesis of viral components and stranded DNA viral genome is complementary to viral mRNA viral genome has the same
enzymes for viral replication & assembly  8 different segments of single stranded RNA associated with sequence as viral mRNA
 Can be either DNA/RNA, single/double-stranded nucleoproteins  2 identical copies of single
 Each RNA segment is packed with 3 polymerase proteins stranded RNA bound to
which come together to form an RNA-dependent RNA nucleocapsid proteins
polymerase enzyme complex which replicates and transcribes
the viral genome in the host cell
Capsid  Icosahedral  Present.  Present, conical shaped
 Protein coat that surrounds and protects viral genome capsid head Enzymes reverse transcriptase,
 Comprise subunits called capsomeres integrase and protease found in
capsid
Envelope  Absent  Glycoproteins embedded in envelope: haemagglutinin (80%) &  Glycoprotein embedded in
 Phospholipid bilayer surrounding the nucleocapsid neuraminidase (20%) envelope: gp41
 Derived from host cell membrane gp120 is attached to gp41
 Embedded with viral glycoproteins involved in host cell recognition
                    Icosahedral capsid head
     containing double                                                                   2 copies of single
  stranded DNA genome Reverse transcriptase stranded RNA genome,
Haemagglutinin
  Envelope each associated with
  Neuraminidase nucleocapsid proteins
 
  Collar
  Tail surrounded
by contractile Capsid
  sheath
8 RNA segments,
  each associated with
1) an RNA dependent Matrix proteins
  Base plate Integrase
RNA polymerase
  2) nucleoproteins
 
  Envelope
Protease
Tail fibre Capsid
 
Tail pin
  gp41
  gp120
                                  T4 phage Lambda phage Influenza Virus Human Immunodeficiency Virus
 
Antigenic Drift and Antigenic Shift
Antigenic Drift : When the influenza virus replicates in its host cell, mutations frequently occur due to the poor proofreading mechanism of the viral RNA-dependent DNA polymerase. Over time,
there is an accumutation of mutations in the viral genome. Sometimes, these mutations produce viruses with modified antigens (e.g. glycoproteins such as haemagglutinin or neuraminidase). If these
viruses infect a host that does not have the antibodies that recognise these modified antigens, the host becomes susceptibleto the virus.

Antigenic Shift: When a bird strain of influenza A and human strain of influenza A infect a single cell of an intermediate host (e.g.a pig), genetic reassortment can occur. Thus when new viruses
are assembled in the host cell, they can have new combinations of RNA segments. Sometimes, genetic reassortment produces viruses with new antigens (e.g. glycoproteins such as haemagglutinin or
neuraminidase). If these viruses infect a human host that does not have the antibodies that recognise these modified antigens, the host becomes susceptibleto the virus.

  Prepared by: Mrs Selvamani Nair, Mdm Sharon Cross and Mrs Wong Seok Hui Raffles Institution 1
Genetics and Inheritance (9744) Viruses 2017
Virus Life Cycle
Stages Bacteriophage Enveloped animal viruses
T4 phage Lambda phage Influenza HIV
(Lytic phage) (Temperate phage)
1. Attachment  Attachment sites on tail fibres adsorbs to complementary Enveloped viruses use viral glycoproteins to bind to specific receptor molecules on host cell.
Virus receptor sites on bacterial surface (e.g. E.coli)  Hemagglutinin binds to complementary  gp120 binds to complementary CD4 receptors on T
recognises and sialic acid receptor on host cell (e.g. helper cells or (macrophages) with the help of a co-
attaches to epithelial cells in respiratory tract) receptor.
host cell membrane
2. Penetration  Bacteriophage releases lysozyme which digests bacterial Release of capsid into host cell cytosol
Viral genome cell wall  Virus enters host cell by endocytosis (the  With the help of gp41, the viral envelope fuses with
introduced  This allows the release of molecules from the bacterium process involves invagination of membrane) host cell membrane  nucleocapsid is released into
into host cell which triggers a change in shape of the proteins in the base  Endocytic vesicle fuses with lysosome  cytosol
plate which causes the contraction of tail sheath which will which lowers the pH  causes viral envelope
drive the hollow core tube through cell wall to fuse with lipid bilayer of vesicle 
 When the tip of the hollow core tube reaches the plasma nucleocapsid is released into cytosol
membrane, phage DNA is injected into the bacterial cell (NB: HIV can also enter by endocytosis)
 The empty capsid remains outside Degradation of capsid to release viral genome (uncoating)
Capsid degraded by cellular enzymes and the Capsid degraded by cellular enzymes the 2 viral RNA
8 viral RNA segments that are released into strands and enzymes are released into the cytosol
cytosol enter the nucleus
3. Replication  Host cell  Linear phage DNA circularizes  Viral RNA-dependent RNA polymerase uses  Reverse transcriptase makes DNA strand using viral
Synthesis of macromolecular and inserted into host cell viral genome as a template to synthesise RNA as template to form a DNA-RNA hybrid. The RNA is
viral synthesizing genome by enzyme integrase mRNA then degraded and the 2nd DNA strand is made 
components & machinery is used  The integrated phage DNA is  mRNA double-stranded DNA molecule produced
viral genome to synthesise phage known as a prophage 1. enters cytosol translated into viral  Viral DNA enters nucleus  inserted into host cell
replication proteins  Expression of phage genes is structural components (Capsid proteins are genome by integrase  Viral DNA known as provirus
 Early phage repressed by phage repressor made in the cytosol. Envelope glycoproteins can remain latent for a long time
proteins: degrade proteins. Hence new phages are made in the RER & eventually are  Upon activation, viral DNA transcribed to viral RNA
host DNA are not synthesized embedded in host cell membrane) which enters cytosol
 Phage DNA  Prophage replicates along with 2. can also act as template for synthesis of new  Viral RNA can either act as mRNA and be translated into
synthesized using bacterial chromosome viral RNA genome in the nucleus. Viral RNA proteins or become part of the genome of the new virions
host cell nucleotides  During spontaneous induction, genome then exits nucleus.  mRNA
and early proteins cellular proteases are activated. 1. is translated to viral polyproteins
 Late phage They destroy the repressor 2. is translated into envelope glycoproteins gp120 and gp
proteins: are phage proteins 41 in the RER and eventually are embedded in the host
enzymes and  The prophage is then excised cell surface membrane.
structural from the bacterial genome
components  The replication phase of lytic
cycle then occurs.(see left)
4.Maturation  Phage DNA and capsid assemble into a DNA-filled head  Capsid proteins associate with host cell For HIV, maturation is completed only after release
Assembly of  Head, tail and tail fibers assembled independently & join in a membrane where viral glycoproteins are of virus.
complete specific sequence. inserted.  The viral RNA genome and polyprotein assembles at
viruses  Nucleoproteins associate with the RNA the cell surface membrane where viral glycoproteins
genome and then interact with capsid proteins have been inserted.
that have associated with the glycoproteins
embedded on the plasma membrane.
 This initiates the budding process.
5. Release  Phage lysozyme synthesised within the cell breaks down  Newly formed viruses bud off by evagination,  Newly formed viruses bud off by evagination, acquiring
the bacterial cell wall acquiring host cell membrane with embedded host cell membrane with embedded viral glycoproteins
 Bacterial cell membrane lyses and release the newly formed viral glycoproteins  Viral protease cleaves polyproteins, forming viral
virions  Neuraminidase facilitates the release of the enzymes and proteins.
new virions from the host cell membrane by  The viral RNA genome and enzymes are then
cleaving sialic acid from the host cell receptor. encapsulated by a protein coat to form a capsid
 The mature HIV virus (virion) is now able to infect
neighbouring cells.

  Prepared by: Mrs Selvamani Nair, Mdm Sharon Cross and Mrs Wong Seok Hui Raffles Institution 2
Genetics and Inheritance (9744) Viruses 2017
Influenza Life Cycle HIV Life Cycle
(1) Hemagglutinin (5) Newly formed viruses bud off by evagination, (2a) With the help of
(2a) Virus enters host (1) gp120 binds to
recognizes & binds to acquiring host cell membrane with embedded gp41, the viral
cell by endocytosis CD4 receptors on T
sialic acid receptor on viral glycoproteins. Neuraminidase facilitates (1) envelope fuses
(which involves lymphocytes (or
host membrane the release of the new virions from the host cell with host cell
macrophages) with the
invagination of membrane. Host cell may or may not be lysed. membrane 
help of a co-receptor. (2a & b)
(1) membrane) nucleocapsid is
(5) (3a) Reverse transcriptase released into cytosol
makes DNA strand using viral
RNA as template  RNA (2b) Capsid
(3a) Viral RNA
degraded  2 nd
DNA strand degraded  viral
(4) Nucleoproteins Reverse
made  double-stranded RNA and
(2b) Endocytic associate with the RNA transcriptase RNA-DNA
DNA molecule (ds DNA) enzymes
vesicle fuses with (4) genome and then transcribes RNA hybrid
released into
lysosome  which (2a) produced
into DNA
interact with capsid cytosol
lowers the pH  ds DNA
causes viral envelope proteins that have
(3b) Viral DNA enters
to fuse with lipid associated with the nucleus  inserted into host (5) Newly formed
bilayer of vesicle  glycoproteins cell genome by integrase  viruses bud off
Translation
nucleocapsid is embedded on the Viral DNA known as provirus (3b) by evagination,
integrase integrates acquiring host
released into cytosol plasma membrane. This can remain latent for a long DNA into genome cell membrane
(2b) Lysosome initiates the budding time
with embedded
process. (3c) Upon activation, viral viral
DNA is transcribed to viral glycoproteins.
(3bii) RNA which enters cytosol Viral protease
  (2c) (3bi) Viral
Viral RNA can either act as
RNA (3c) cleaves
  mRNA mRNA and be translated into activation
polyproteins,
  (2c) Capsid degraded by proteins or become part of the Viral RNA forming viral
cellular enzymes and viral (3a) (3bi) mRNA can used genome of the new virions. enzymes and
  RNA enters nucleus as a template for proteins.
  synthesis of new viral (3d) mRNA is translated to (3d) The viral RNA
(3a) Viral genome used as a Viral RNA
RNA genome in the 1. viral polyproteins genome and
Note: translation
  Only 2 out of the 8 RNA
template for mRNA synthesis by
nucleus 2. envelope glycoproteins enzymes are
RNA-dependent RNA gp120 and gp 41 in polyproteins Viral genome
  segments are shown
polymerase.
then
the RER which protease encapsulated by
  due to space
(3bii)mRNA then enters cytosol eventually are embedded proteins a protein coat to
constraints in the
 translated into viral structural in the host cell surface (4 & 5) form a capsid.
diagram)
components (Capsid proteins are membrane. The mature HIV
made in the cytosol. Envelope virus (virion) is
(4) Viral RNA genome and
glycoproteins are made in the now able to
polyprotein assemble at the cell
RER & are eventually embedded infect
surface membrane where viral
in host cell membrane) neighbouring
glycoproteins have been inserted.
cells.

Pathogenecity of Influenza Pathogenecity of HIV

When influenza will bind to sialic acid receptors on epithelial cells of respiratory tract When HIV binds to CD4 receptor on a T helper cell, a type of T lymphocyte
 
Influenza replicates within it and then buds off. Infected epithelial cells eventually lyse HIV replicates within it and then buds off. Infected T helper cells eventually lyse.
 
The build up of dead epithelial cells results in inflammation and symptoms of influenza appear With fewer T helper cells, the immune system is depressed & individuals are more susceptible to
runny nose & scratchy throat opportunistic infections. When infections become unmanageableAIDS  death

The epithelial layer weakens and the individual is more susceptible to bacterial infections like  Virus able to avoid detection by immune system as it mutates at a high rate during replication
pneumonia surface proteins altered prevent recognition & elimination by immune system
 Treatment:1) antibiotics for bacterial infections  Treatment: drug cocktail that targets (1) enzymes(RIP) i.e. enzyme inhibitors
2) antiviral drugs which target viral enzymes i.e enzyme inhibitors (2) glycoproteins (gp120) i.e. entry inhibitors
e.g:Tamiflu for some strains of influenza

  Prepared by: Mrs Selvamani Nair, Mdm Sharon Cross and Mrs Wong Seok Hui Raffles Institution 3
Genetics and Inheritance (9744) Viruses 2017
Life Cycle of Lytic Phage (e.g. T4)

 
Life Cycle of Temperate Phage (e.g. Lambda)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  Prepared by: Mrs Selvamani Nair, Mdm Sharon Cross and Mrs Wong Seok Hui Raffles Institution 4