Download Chapter 6 An Introduction to Viruses

Chapter 6
An Introduction to Viruses
Introduction
All life-forms can be infected by viruses.
Some viruses generate serious epidemics, from dengue fever to
influenza to AIDS.
Others fill essential niches in the environment, particularly in marine
ecosystems.
In research, viruses have provided both tools and model systems in
molecular biology.
This 11-inch-high limestone Egyptian
funerary stele is from Saqqara, 10 miles
south of Cairo; Amarna Period, 18th Dynasty
(1403-1365 BCE), Glyptotek Museum,
Copenhagen.
The stele portrays Roma (or Rema), an
Egyptian doorkeeper, and his family giving
offerings to the Goddess Astarte.
Thought to be the earliest depiction of a
victim of poliomyelitis, the man adeptly
carries a goblet while supporting himself
with a staff.
His withered right leg and deformed right
foot are characteristic of poliomyelitis.
Ramses V, Pharaoh of Egypt
He died ~1145 BCE, presumably
of smallpox. His mummified
head and torso bear the
characteristic lesions of the
disease.
Smallpox victims included many
other rulers throughout history,
among them Louis XV of France,
Mary II of England, and the
Holy Roman Emperor Joseph I.
The search for the elusive virus
Louis Pasteur postulated that rabies was caused by a virus (1884)
Ivanovski and Beijerinck showed a disease in tobacco was caused by a
virus (1890s)
1950s virology was a multifaceted discipline
Viruses: non-cellular particles with a definite size, shape, and
chemical composition
Viral diseases led to the development of some of the first vaccines
Poliovirus causes poliomyelitis, which can lead to paralysis
President Franklin Roosevelt established the March of Dimes
With its support, Jonas Salk developed the first polio vaccine in 1952
What Is a Virus?
A virus is a non-cellular particle that must infect a host cell, where it
reproduces.
It typically subverts the cell’s machinery and directs it to produce viral
particles.
The virus particle, or virion, consists of a single nucleic acid (DNA or
RNA) contained within a protective protein capsid.
The Position of viruses in the biological spectrum
There is no universal
agreement on how and when
viruses originated
Viruses are considered the
most abundant microbes on
earth
Viruses played a role in the
evolution of Bacteria,
Archaea, and Eukarya
Viruses are obligate
intracellular parasites
Viruses infect all forms of life
Viruses are ubiquitous in all environments
Viruses are part of our daily lives
Most frequent infections of college students:
1) Respiratory pathogens such as rhinovirus (the common cold) and
Epstein-Barr virus (infectious mononucleosis)
2) Sexually transmitted viruses such as herpes simplex virus (HSV) and
papillomavirus (genital warts)
Different viruses infect every group of organisms
Each species of virus infects a particular group of host species, or host
range
Viroids
Viroids are RNA molecules that infect plants.
They have no protein capsid.
Are replicated by host RNA polymerase.
Some have catalytic ability.
Prions
Prions are proteins that infect animals.
They have no nucleic acid component.
Have an abnormal structure that alters the conformation of other
normal proteins
Extremely resistant to usual sterilization techniques
Prions Diseases
Common in animals
Scrapie in sheep and goats
Bovine spongiform encephalopathies (BSE), a.k.a. mad cow disease
- transmissible and fatal neurodegenerative disease
Humans – Creutzfeldt-Jakob Syndrome (CJS)
Viral structure
Viruses bear no resemblance to cells
Lack protein-synthesizing machinery
Viruses contain only the parts needed to invade and control a host cell
Virus Structure
The viral capsid is the protein shell of a virus.
The capsid encloses the viral genome
The capsid delivers the viral genome into the host cell.
Different viruses make different capsid forms.
Capsids
All viruses have capsids (protein coats
that enclose and protect their nucleic
acid)
The capsid together with the nucleic
acid is the nucleocapsid
Each capsid is made of identical
protein subunits called capsomers
Some viruses have an external
covering called an envelope; those
lacking an envelope are naked
Structural types of capsids
Helical – Rod or thread-like continuous helix of capsomers forming a
cylindrical nucleocapsid
Structural types of capsids
Icosahedral - Polyhedral with 20 identical triangular faces
Have a structure that exhibits rotational symmetry
Envelope
In some icosahedral viruses, the capsid is enclosed in an envelope,
formed from the cell membrane.
The envelope contains glycoprotein spikes, which are encoded by the
virus. Spikes are essential for attachment of the virus to the host cell
Between the envelope and capsid, tegument proteins may be found.
Viruses lacking an envelope are naked
Dr.Stepehen Fuller
Functions of Capsid
1. Protect genome from atmosphere (May include damaging UV-light,
shearing forces, nucleases either leaked or secreted by cells).
2. Virus-attachment protein- interacts with cellular receptor to initiate
infection.
3. Delivery of genome in infectious form. May simply “dump” genome
into cytoplasm (most +ssRNA viruses) or serve as the core for
replication (retroviruses and rotaviruses).
Viruses with complex structures
These have complex multipart structures
T4 bacteriophages: Have an icosahedral “head” and helical “neck”
Poxviruses lack a typical capsid and are covered by a dense layer of
lipoproteins
Types of Viruses
Nucleic Acids
Viral genome – either DNA or RNA but never both
Carries genes necessary to invade host cell and redirect cell’s activity
to make new viruses
Number of genes varies for each type of virus – few to hundreds
Nucleic Acids
• DNA viruses
Usually double stranded (ds) but may be single stranded (ss)
Circular or linear
• RNA viruses
Usually single stranded, may be double stranded, may be segmented
into separate RNA pieces
ssRNA genomes ready for immediate translation are positive-sense
RNA
ssRNA genomes that must be converted into proper form are negativesense RNA
Viral enzymes
• Pre-formed enzymes may be present
– Polymerases – DNA or RNA
– Replicases – copy RNA
– Reverse transcriptase – synthesis of DNA from RNA (AIDS virus)
Bacteriophage replication
All viruses require a host cell for reproduction.
Thus, they all face the same needs for host infection:
Host recognition and attachment
Genome entry
Assembly of progeny virions
Exit and transmission
Multiplication cycle in Bacteriophages
Bacteriophages – bacterial viruses (phages)
Most widely studied are those that infect Escherichia coli – complex
structure, DNA
Multiplication goes through similar stages as animal viruses
Only the nucleic acid enters the cytoplasm - uncoating is not
necessary
Release is a result of cell lysis induced by viral enzymes and
accumulation of viruses - lytic cycle
Steps in phage replication
1.
Adsorption – binding of virus to specific molecules on host cell
2.
Penetration – genome enters host cell
3.
Replication – viral components are produced
4.
Assembly – viral components are assembled
5.
Maturation – completion of viral formation
6.
Lysis & Release – viruses leave the cell to infect other cells
Bacteriophages attach to host cells
Contact and attachment are mediated by cell-surface receptors.
Proteins that are specific to the host species and which bind to a
specific viral component.
Bacterial cell receptors are normally used for important functions for
the host cell. Example: sugar uptake
Phage reproduction within host cells
Most bacteriophages (phages) inject only their genome into a cell
through the cell envelope.
The phage capsid remains outside, attached to the cell surface.
It is termed a “ghost.”
Bacteriophages can undergo two different types of life cycles
1) Lytic cycle
Bacteriophage quickly replicates, killing host cell
2) Lysogenic cycle
Bacteriophage is quiescent.
Integrates into cell chromosome, as a prophage
Can reactivate to become lytic
The “decision” between the two cycles is dictated by environmental
cues
In general, events that threaten host cell survival trigger a lytic burst
Lysogeny: The Silent Virus Infection
• Not all phages complete the lytic cycle
• Some DNA phages, called temperate phages, undergo adsorption
and penetration but don’t replicate
• The viral genome inserts into bacterial genome and becomes an
inactive prophage – the cell is not lysed
• Prophage is retained and copied during normal cell division
resulting in the transfer of temperate phage genome to all host cell
progeny – lysogeny
• Induction can occur resulting in activation of lysogenic prophage
followed by viral replication and cell lysis
Lysogeny
• Lysogeny results in the spread of the virus without killing the host
cell
• Phage genes in the bacterial chromosome can cause the production
of toxins or enzymes that cause pathology – lysogenic conversion
– Corynebacterium diphtheriae
– Vibrio cholerae
– Clostridium botulinum
Multiplication of Bacteriophage
Animal Virus replication cycles
The primary factor determining the life cycle of an animal virus is the
form of its genome.
DNA viruses
Can utilize the host replication machinery
RNA viruses
Use an RNA-dependent RNA-polymerase to transcribe their mRNA
Retroviruses
Use a reverse transcriptase to copy their genomic (RNA) sequence
into DNA for insertion in the host chromosome
Modes of animal viral multiplication
General phases in animal virus multiplication cycle:
1.Adsorption – binding of virus to specific molecules on the host cell
2.Penetration – genome enters the host cell
3.Uncoating – the viral nucleic acid is released from the capsid
4.Synthesis – viral components are produced
5.Assembly – new viral particles are constructed
6.Release – assembled viruses are released by budding (exocytosis) or
cell lysis
Animal viruses show tissue tropism
Animal viruses bind specific receptor proteins on their host cell.
Receptors determine the viral tropism.
Ebola virus exhibits broad tropism, infecting many kinds of
host tissues.
Papillomavirus shows tropism for only epithelial tissues.
Most animal viruses enter host as virions.
Internalized virions undergo uncoating, where genome is released
from its capsid.
Adsorption and host range
• Virus coincidentally collides with a susceptible host cell and adsorbs
specifically to receptor sites on the membrane
• Spectrum of cells a virus can infect – host range
– Hepatitis B – human liver cells
– Poliovirus – primate intestinal and nerve cells
– Rabies – various cells of many mammals
Envelope spike
Host cell membrane
Capsid spike
Receptor
Host cell
membrane
Receptor
Penetration/Uncoating
• Flexible cell membrane is penetrated by the whole virus by:
– Endocytosis – entire virus is engulfed and enclosed in a vacuole
or vesicle
– Fusion – envelope merges directly with membrane resulting in
nucleocapsid’s entry into cytoplasm
Variety in Penetration and Uncoating
Replication and protein production
• Varies depending on whether the virus is a DNA or RNA virus
• DNA viruses generally replicate and assemble in the nucleus
• RNA viruses generally replicate and assemble in the cytoplasm
– Positive-sense RNA contain the message for translation
– Negative-sense RNA must be converted into positive-sense
message
Papillomavirus (DNA) Life Cycle
HPV, a double-stranded DNA virus,
enters the cytoplasm, where the
protein coat disintegrates. The viral
DNA enters the nucleus for replication
and transcription by host polymerases.
Viral mRNA returns to the cytoplasm
for translation of capsid proteins,
which return to the nucleus for
assembly of virions.
Picornavirus (RNA) Life Cycle
Picornavirus life cycle. A picornavirus
inserts its (+) strand RNA into the
cell. Reproduction occurs entirely in
the cytoplasm. A key step is the early
translation of a viral gene to make
RNA-dependent RNA polymerase.
The polymerase uses the
picornavirus RNA template to make
(–) strand RNA, which then serves as
a template for other viral mRNAs, as
well as progeny genomic RNA, which
is replicated in virus-induced vesicles
from the endoplasmic reticulum.
HIV (Retrovirus) Life Cycle
Release
• Assembled viruses leave the host cell in one of two ways:
– Budding – exocytosis; nucleocapsid binds to membrane which
pinches off and sheds the viruses gradually; cell is not
immediately destroyed
– Lysis – nonenveloped and complex viruses released when cell
dies and ruptures
Damage to host cell
Cytopathic effects - virus-induced damage to cells
1.
Changes in size and shape
2.
Cytoplasmic inclusion bodies
3.
Inclusion bodies
4.
Cells fuse to form multinucleated cells
5.
Cell lysis
6.
Alter DNA
7.
Transform cells into cancerous cells
Effects of some human viruses
Persistent infections
Persistent infections - cell harbors the virus and is not immediately
lysed
Can last weeks or host’s lifetime; several can periodically reactivate –
chronic latent state
Measles virus – may remain hidden in brain cells for many years
Herpes simplex virus – cold sores and genital herpes
Herpes zoster virus – chickenpox and shingles
Viral damage
• Some animal viruses enter the host cell and permanently alter its
genetic material resulting in cancer – transformation of the cell
• Transformed cells have an increased rate of growth, alterations in
chromosomes, and the capacity to divide for indefinite time periods
resulting in tumors
• Mammalian viruses capable of initiating tumors are called
oncoviruses or oncogenic viruses
– Papillomavirus – cervical cancer
– Epstein-Barr virus – Burkitt’s lymphoma
– Hepatitis C virus – Liver cancer
Oncogenic viruses
Oncogenic viruses transform the host cell to become cancerous.
Mechanisms of oncogenesis include:
1) Insertion of an oncogene into the host genome
2) Integration of the entire viral genome
3) Expression of viral proteins that interfere with host cell cycle
regulation
Techniques in cultivating and identifying animal viruses
Methods used:
– Cell (tissue) cultures – cultured cells grow in sheets that support
viral replication and permit observation for cytopathic effects
– Bird embryos – incubating egg is an ideal system; virus is injected
through the shell
– Live animal inoculation – occasionally used when necessary
Methods for growing viruses
Tissue culture of animal viruses
Animal viruses can be cultured within whole animals by serial
inoculation
Ensures that the virus strain maintains its original virulence, but
process is expensive and laborious.
They can also be grown in human cell tissue culture.
Plaque assay of bacteriophages
Plaque assay of animal viruses
Medical importance of viruses
• Viruses are the most common cause of acute infections
• Several billion viral infections per year
• Some viruses have high mortality rates
• Possible connection of viruses to chronic afflictions of unknown
cause
• Viruses are major participants in the earth’s ecosystem
Detection and treatment of animal viral infections
• More difficult than other agents
• Consider overall clinical picture
• Take appropriate sample
– Infect cell culture – look for characteristic cytopathic effects
– Screen for parts of the virus
– Screen for immune response to virus (antibodies)
• Antiviral drugs can cause serious side effects
Other noncellular infectious agents
Satellite viruses – dependent on other viruses for replication
Adeno-associated virus – replicates only in cells infected with
adenovirus
Delta agent – naked strand of RNA expressed only in the presence
of hepatitis B virus