Viral Genetics and Replication
SAMUEL AGUAZIM, M.D.
Lange Chapter 30
NATURE OF Viral GENOMES

RNA or DNA

SEGMENTED OR NON-SEGMENTED

Double stranded or single stranded
GENETIC CHANGE

MUTATION

RECOMBINATION
MUTATIONS
- A mutation
is a change in the base
sequence of DNA
-insertion of a different amino acid into a
protein and the appearance of an altered
phenotype.
Mutations result from three types of
molecular changes:
1. Base substitution: one base is inserted in the
place of another.
2. Frame shift mutation: One or more base pairs are
added or deleted.
3. When transposons or inserted sequences are
integrated into DNA.
RECOMBINATION


it is the exchange of genes between two
chromosomes that is based on crossing over
within regions of significant base sequence
homology.
It can be readily demonstrated for viruses
with double stranded DNA as the genetic
material and has been used to determine
their genetic map.
REASSORTMENT

Occurs among viruses with segmented genomes.

Mixing of genome segments into new sets.

Results in reassorted viruses which display properties
(antigenicity, pathogenicity, etc.) differing from either
parent.

Especially important to epidemiology of influenza
viruses.
REASSORTMENT
ORTHOMYXOVIRUSES
M2 -Human
HA - Human
NA - Human
helical nucleocapsid
Human
lipid bilayer membrane
polymerase complex
(human)
M1- Human
ORTHOMYXOVIRUSES
HA (bird)
NA (bird)
helical nucleocapsid
(bird)
lipid bilayer membrane
polymerase complex
(bird)
M1 protein (bird)
ORTHOMYXOVIRUSES
HA (Human)
HA (bird)
NA (bird)
helical nucleocapsid
(bird)
lipid bilayer membrane
polymerase complex
(bird)
HA (Human)
M1 protein (bird)
Non-genetic interactions:
Complementation:


Sharing of gene products (proteins) between
two mutant viruses each virus unable to
replicate alone.
On infection of same cell, each produces a
‘good’ protein that is mutated in the other
virus thus providing normal copies of all
necessary gene products, mutant viral
genome can be replicated and progeny
viruses are produced.
Yz
yZ
Phenotypic mixing:
a.Packaging of genome of one type of virus into
capsid of another type of virus to create
‘pseudotypes’.
b.Pseudotype virus has surface properties of one
virus (receptor recognition and antigenicity, for
example) but has the genome of a different
virus.
PHENOTYPIC MIXING
no changes in genome
PHENOTYPIC MIXING
Viral Replication Outcomes
1.Lytic infection:- virus replication in cell produces progeny
virus particles, cell dies as a result.
2.Latent infection:- infected cell contains viral genome but it
is not being expressed, no virus produced. The cell is not
killed. Viruses can become reactivated and produce
progeny virus.
3.Persistent infection: virus replicates continuously in cell
and cell remains viable.
4.Transformation: virus encodes a gene product that alters
the cell so that it is transformed into a cancerous or
immortalized state.
Steps in
viral
replication.
Steps in viral replication
1. Attachment or adsorption
Interaction of part of virus (surface glycoprotein,
individual protein or mosaic of proteins) with
receptor on cell surface.
HOST-CELL RECEPTORS FOR VIRUSES
Virus
Receptor
Polio……………......Ig superfamily protein
Rabies ……………..Acetlycholine receptor
Herpes……………...FGF receptor
HIV………………...CD4 molecule
Influenza A…….…. Sialic acid
Paramyxoviruses......Sialic acid
SOME VIRAL STRUCTURES USED FOR
ATTACHMENT TO CELLS
1. Surface glycoproteins: many viruses;
examples-HIV, influenza, measles.
2. Fibers: projecting from the surface of
adenovirus.
3. A single protein: on the surface of a
capsid.
4. A mosaic: of several proteins, forming a
binding-site, as in the picornaviruses.
2.
Penetration or entry:

Entry refers to entry of virus into cell.

Entry may occur by direct fusion of the viral
membrane and the plasma membrane of the cell.
These viruses have surface glycoproteins which
promote membrane fusion.
Entry may occur through receptormediated endocytosis:

Virus particle ends up in cytoplasm inside an
endosome, which has a low pH.

The acidic environment activates a viral
glycoprotein which then causes fusion between
the viral membrane and the membrane of the
endosome with the
release of the viral
genome into the cytoplasm.
Binding
Reverse transcription
Integration
Transcription
Nuclear localization
Splicing
endosome
RNA export
Genomic RNA
Modification
mRNA
Translation
Assembly
Budding
Maturation
3. Uncoating:

is the release of the viral genome (or a subviral
structure containing the viral genome) from the
virus particle.

This process may occur in the cytoplasm or the
nucleus.
4. Synthetic phase: (transcription,
translation & replication)
a.
Transcription of viral genome:
i) All RNA viruses encode a transcriptase; the transcriptase may be part of viral
structure



ss (-) RNA produces mRNA.
ss (+) RNA acts as it’s own mRNA
vRNA produces mRNA
b. Translation: viral mRNAs are translated using cellular ribosomes.
c. Replication: production of viral genome.
i) All DNA viruses (except poxviruses) replicate in the nucleus.
ii) All RNA viruses [except influenza viruses and retroviruses] replicate in
the cytoplasm.
5. Assembly:
a. Newly synthesized molecules are assembled
into progeny virus particles.
6. Release:
a. Newly synthesized molecules are release by
budding forming envelope or by cytolysis with no
envelope.
DNA Non Enveloped
Virus