Viruses: small but not simple

Wed 15 Oct 2008, Guest Lecture: Susi Remold

 Outline
Viruses are small
Virus structure and components
Virus life cycles
Effects on cells and on hosts
Physical size: Size text
• Smallest infectious agents
• Most can only be seen with electron microscopy
• Animal viruses
– Proviruses- around 20 nm in diameter
– Mimiviruses- up to 450 nm in length

Genome size:
•Like physical size, genome size overlaps with bacteria
•Animal viruses
–Hepadnavirus- 3200 bp (less than one page of text!)
–Mimiviruses- 1.2 million bp
 Relative physical size

Figure 6.1
Relative genome size
 Viruses were discovered late
• Viruses were too small to be seen with the first
microscopes
• The cause of viral infections was unknown for
years
• Louis Pasteur first proposed the term virus
• 1890s
– Ivanovski and Beijerinck showed that a disease in
tobacco was caused by a virus
– Loeffler and Frosch discovered an animal virus that
causes foot –and-mouth disease in cattle
• Many years of experimentation showed what we
know today and by the 1950s virology had grown
Properties
 Outline
Viruses are small
Virus structure and components
•Envelope
•Capsid
•Nucleic acid
•other
Virus life cycles
Effects on cells and on hosts
 The Viral Envelope
• Enveloped viruses take a bit of the host cell
membrane in the form of an envelope

• In the envelope, viral proteins replace some or

all cell membrane proteins

• Some proteins form a binding layer between the

envelope and the capsid

• Glycoproteins remain exposed as spikes

(peplomers)- essential for attachment
 Naked and Enveloped Viruses
Many structural similarities
Differ in how they interact with the host cell
Differ in sensitivity to environmental damage (naked often harder to destroy)
 Functions of the Viral
Capsid/Envelope
For virus:
• Protects nucleic acids
• Help introduce the viral DNA or RNA into a
suitable host cell
For us:
• Stimulate the immune system to produce
antibodies that can protect the host cells
against future infections
 The Viral Capsid
• Protects the nucleic acid, determines shape
• Constructed from identical protein subunits
called capsomers
• Two common types
Helical
• Rod-shaped capsomers
• Assemble in to helical nucleocapsid
Icosahedral
• Three-dimensional, 20-sided figure with 12
evenly spaced corners
• Although they all display this symmetry, there
are wide variations
 Helical
capsids

Figure 6.5
 Tobacco mosaic virus:
Without envelope

Influenza virus:
With envelope

Figure 6.6
 Icosahedron formation
Triangular faces of an icosahedron…

… assembled to make the capsid

Figure 6.7
 Icosahedron examples

Papillomavirus (without envelope) Herpesvirus (with envelope)

Figure 6.8
 Other cool shapes!!

Figure 6.9
 Nucleic Acids
• Genome- the sum total of the genetic
information carried by an organism
• Number of viral genes compared with a cell-
quite small
• They only have the genes necessary to
invade host cells and redirect their activity
• Some viruses are exceptions to the rules re:
DNA and RNA
– Parvoviruses contain single-stranded DNA
– Reoviruses contain double-stranded RNA
 Example genomes
replication

N PM G L VSV: 5 GENES

capsid envelope protein

HIV: 9 GENES
Red: specific to HIV

capsid
envelope proteins
replication
 DNA Viruses
• ssDNA
• dsDNA
– linear
– circular
 RNA Viruses
• Mostly single-stranded
– Positive-sense RNA: genomes that are ready
for immediate translation into proteins
– Negative-sense RNA: genomes have to be
converted into the proper form to be made
into proteins
• Segmented- individual genes exist on
separate pieces of RNA
Other Substances in Virus Particles
Nucleoproteins (help pack the nucleic acid)
Enzymes for use within the host cell
– Polymerases to synthesize DNA and RNA
– Replicases to copy RNA
P L envelope
Why does VSV need P
and L, which make up
the RNA replicase to
be packaged in the
virus particle?

N-subunit
RNA G M
 Outline
Viruses are small
Virus structure and components
Virus life cycles
•Adsorption
•Penetration
•Uncoating
•Synthesis
•Assembly
•Release
Effects on cells and on hosts
 The host cell
is necessary
for viral
multiplication

Entire length of
cycle- anywhere from
8 to 36 hours

Figure 6.11
 Adsorption
• Virus encounters susceptible host cells
• Adsorbs specifically to receptor sites on
the cell membrane
• Because of the exact fit required, viruses
have a limited host range
Figure 6.12
 Penetration
• Flexible cell membrane of the host is
penetrated by the whole virus or its nucleic
acid
• Endocytosis: entire virus engulfed by the
cell and enclosed in a vacuole or vesicle
• The viral envelope can also directly fuse
with the host cell membrane
Figure 6.13
 Uncoating
• Enzymes in the vacuole dissolve the
envelope and capsid
• The virus is now uncoated
 Synthesis
• Free viral nucleic acid exerts control over the
host’s synthetic and metabolic machinery
• DNA viruses- enter host cell’s nucleus where
they are replicated and assembled
• RNA viruses- replicated and assembled in
the cytoplasm
• Details depend on the type of nucleic acid, its
orientation and the replication machinery
Replication of DNA viruses

Can integrate into the host DNA (example:

Herpesvirus)

… or not integrate (example: Pox viruses)

Often use the host DNA polymerases

mRNA is made from the viral genomic DNA,

much as occurs for host DNA
3 RNA-virus strategies

+RNA:Host “sees” an mRNA and can

be directly transcribed. (example:
Coronavirus (SARS))

-RNA:Virus particle must contain an

RNA polymerase to get the process going.
Once the first +strand is made, virus can
use host machinery. (example: rabies)

Retroviruses: A reverse
transcriptase makes a DNA molecule using
the RNA virus template. This DNA copy
can be integrated into the host genome
(example: HIV)
 Assembly
• Mature virus particles are constructed from
the growing pool of parts

• NOT like reproduction of cells, where one

offspring made at a time

• Often happens near the site of release

 Release
• Nonenveloped and complex viruses are
released when the cell lyses or ruptures
• Enveloped viruses are liberated by
budding or exocytosis
• Anywhere from 3,000 to 100,000 virions
may be released, depending on the virus
Figure 6.15
 Outline
Viruses are small
Virus structure and components
Virus life cycles
And then there are the Bacterial viruses!

Effects on cells and on hosts

 Viruses that Infect Bacteria
• Bacteriophage
• Most contain dsDNA
• Sometimes make the bacteria they infect
more pathogenic for humans

• The challenge they face:

How to get past the bacterial cell wall??
 How to get past the cell wall

Figure 6.18
 Details differ,
general story
is the same:

Adsorption
Penetration
Uncoating
Synthesis
Assembly
Release

Figure 6.17
 Lysogeny: stall between uncoating
and replication
• Temperate phages- special DNA phages that
undergo adsorption and penetration but are not
replicated or released immediately
• Instead the viral DNA enters an inactive
prophage stage
• Lysogeny: the cell’s progeny will also have the
temperate phage DNA
• Lysogenic conversion: when a bacterium
acquires a new trait from its temperate phage
 Lysogenic phages
integrate into host DNA
much like some animal
DNA and retroviruses

Figure 6.20
 Outline
Viruses are small
Virus structure and components
Virus life cycles
Effects on cells and on hosts
 Damage to the Host Cell and
Persistent Infections
• Cytopathic effects- virus-induced
damage to the cell that alters its
microscopic appearance

• Inclusion bodies- compacted masses of

viruses or damaged cell organelles
Figure 6.16
Figure 6.22
 Medical Importance of Viruses
• Most common cause of acute infections
that do not result in hospitalization
• Most do not cause death but those that do
can have very high mortality rates
• Others can lead to long-term debility
 Unusual effects of virus infection
• Some viral infections maintain a carrier
relationship
– The cell harbors the virus; not immediately lysed
– Persistent infections- from a few weeks to the
remainder of the host’s life
• Some viruses remain in a chronic latent state,
periodically becoming activated
• Some viruses enter their host cell and
permanently alter its genetic material, leading to
cancer
– Oncogenic viruses - effect is called transformation
– Oncoviruses- mammalian viruses capable of
initiating tumors
Treatment of Animal Viral Infections
• Because they are not bacteria, antibiotics are
ineffective

• Antiviral drugs block virus replication by

targeting one of the steps in the viral life cycle

• Interferon shows potential for treating and

preventing viral infections

• Vaccines stimulate immunity