Viral Growth Lec4

Viral Growth (Replication)
ICTV Viral Classification

Replication: Two different ways
Growth curve The second is a

which shows the stepwise
amount of virus description of the
produced at specific events
different times after within the cell
infection during virus growth
One-step growth curve of virus
replication
One-step growth curve of virus
replication
Morphologic and Structural Effects
• 1 The cytopathic effect, or necrosis
Alterations of cell morphology accompanied
by marked derangement of cell function begin
toward the end of the latent period of cells in
the tissue culture (polio-, herpes-, measles-,
adenovirus, cytomegalovirus, etc).
• 2 The inhibition of cellular metabolism, or
failure of virus-infected cells to produce acid
(eg, enteroviruses).
Phage
plaques
Photograph of a plate showing plaques formed by

bacteriophage on a lawn of sensitive bacteria.
The plaques shown are about 1-2 mm in diameter.
The size of the plaque formed depends on the virus,
the host, and conditions of culture.
• 3. The appearance of a hemagglutinin (eg,
mumps, influenza) or complement-fixing
antigen (eg, poliomyelitis, varicella, measles).
• 4 The adsorption of erythrocytes to infected
cells, called hemadsorption (paramfluenza,
influenza). This reaction becomes positive
before cytopathic changes are visible, and in
some cases it is the only means of detecting
the presence of the virus
• 5 Interference by a noncytopathogenic virus
(eg, rubella) with replication and cytopathic effect
of a second, indicator virus (eg, echovirus).
• 6 Morphologic transformation by an oncogenic
virus (eg, SV40, Rous sarcoma virus), usually
accompanied by the loss of contact inhibition and
the piling up of cells into discrete foci Such
alterations are a heritable property of the
transformed cells.
7 Formation of syncytia, or polykaryocytes, which

are large cytoplasmic masses that contain many nuclei
(poly, many; karyon, nucleus).
8 Alteration of cytoskeleton organization by virus
infection.
• 9 Genotoxic Effects (Chromosome damage
may be caused directly by the virus particle or
indirectly by events occurring during synthesis
of new viral macromolecules (RNA, DNA,
protein).
• 10 Inclusion Body Formation (They may be
situated in the nucleus (herpesvirus), in the
cytoplasm (pox virus), or in both (measles
virus)
Gene Expression & Genome
Replication
Baltimore Viral Classification
Important Features of DNA Viruses
Important Features of RNA Viruses
RNA VIRUS STRATEGIES
RNA -> RNA
RNA-dependent RNA polymerase
RNA -> DNA

RNA-dependent DNA polymerase
- reverse transcriptase
Host cell DNA -> RNA

DNA-dependent RNA polymerase
37
Need to make mRNA
PLUS (POSITIVE) SENSE RNA GENOMES
(+ve) sense mRNA AAA
38
Need to make mRNA
MINUS (NEGATIVE) SENSE RNA GENOMES
(-ve) sense genomic RNA
40
Need to make mRNA
MINUS (NEGATIVE) SENSE RNA GENOMES
RNA polymerase must be

packaged in virion.

.
(-ve) sense genomic RNA
41
Need to make mRNA
DOUBLE-STRANDED RNA GENOMES

RNA polymerase must be
packaged in virion.
Double-stranded genomic RNA
42
Need to make mRNA
RETROVIRUSES
Reverse transcriptase must
be packaged in virion. DS DS
DNA DNA
+VE
RNA
43
Aspects of viral mRNA and its
expression in eukaryotic cells
• (1) Viral mRNAs have three attributes in
common with cellular mRNAs:
– on the 5' end there is a methylated GTP
"cap
– on the 3' end there is a tail of [poly(A)
– mRNA is generated by splicing from a larger
transcript of the genome
• 2. Making more than one type of mRNA from the same
piece of DNA by "shifting the reading frame.“
• 3. With some DNA viruses, there is temporal control
over the region of the genome
– only the early region of the genome is
transcribed and, therefore, only certain early
proteins are made.
– One of the early proteins is a repressor of the
late genes; this prevents transcription until the
appropriate time.
• 4. Generation of monocistronic mRNAs that will code
for a single protein from the polycistronic viral genome
• 1. Individual mRNAs are transcribed by starting
at many specific initiation points along the
genome e.g. herpes viruses
• 2. Each segment of genome codes for a single
mRNA e.g. Reo viruses
• 3. RNA genome is translated into one long
polypeptide, which is then cleaved into specific
proteins by a protease e.g. polio viruses
THE INFECTION CYCLE
• The infection cycle was first worked out in
bacteriophages (bacterial viruses).
• Animal virus infections can be either lytic or
lysogenic.
LYTIC VERSUS LYSOGENIC
INFECTION
•In a lytic infection, •Lysogenic infections are
the host cells fills also known as latent
with virions and infections.
bursts. •The viral genome
•The result is cell becomes incorporated
death. into the host cell’s DNA.
•It can remain this
way for an extended
period.
•The host cell lives
Bacteriophages
49
LYTIC VERSUS LYSOGENIC INFECTION
LYSOGENIC INFECTION
The alternatives on infection are integration of the virus DNA into
the host DNA (lysogenization) or replication and release of mature
virus (lysis). The lysogenic cell can also be induced to produce
mature virus and lyse.
Lysogenic conversion
Lysogeny
Promotor Vs Operator
Control of lysogeny
"latency-associated transcripts"
(LATS)
• Noncoding,
• Regulatory RNAs that suppress viral
replication.
• Reactivation of viral replication at a later time
occurs when the genes encoding LATS are
excised
Genetics & Gene Therapy:
• (1) mutations and their effect on replication
and pathogenesis
• (2) the interaction of two genetically distinct
viruses that infect the same cell.
• In addition, viruses serve as vectors in gene
therapy and in recombinant vaccines, two
areas that hold great promise for the
treatment of genetic diseases and the
prevention of infectious diseases.
Mutations
• Viral DNA and RNA occur by the same
processes of base substitution, deletion, and
frameshift
e.g. live, attenuated virus
1. antigenic variants
2. drug-resistant mutants
Conditional lethal mutations are extremely
valuable in determining the function of viral
genes
Interactions
• Two genetically distinct viruses infect a cell,
three different phenomena can ensue
1. Recombination
• is the exchange of genes between two
chromosomes that is based on crossing over
within regions of significant base sequence
homology.
• viruses with double-stranded DNA
• recombination by RNA viruses occurs at a very
low frequency
Reassortment
• viruses with segmented genomes, such as
influenza virus, exchange segments
2. Complementation
• can occur when either one or both of the two
viruses that infect the cell have a mutation
that results in a no
• important method by which a helper virus
permits replication of a defective virus.
• Hepatitis B virus providing its surface antigen
to hepatitis delta virus,
3.Phenotypic mixing
• The genome of virus type A can be coated with
the surface proteins of virus type B
• This phenotypically mixed virus can infect cells as
determined by its type B protein coat. However,
the progeny virus from this infection has a type A
coat; it is encoded solely by its type A genetic
material.
• pseudotypes, which consist of the nucleocapsid
of one virus and the envelope of another

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Viral Growth (Replication)

ICTV Viral Classification

Growth curve The second is a

Photograph of a plate showing plaques formed by

7 Formation of syncytia, or polykaryocytes, which

RNA -> DNA

Host cell DNA -> RNA

(+ve) sense mRNA AAA

(+ve) sense mRNA AAA

(-ve) sense genomic RNA

RNA polymerase must be

(+ve) sense mRNA AAA

DOUBLE-STRANDED RNA GENOMES

(+ve) sense mRNA AAA

Double-stranded genomic RNA

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