Virology, lect. 1.
Impact: It is important to study viruses
because:
•Many important infectious diseases that afflict
humankind are caused by viruses. These can be
fatal, uncomfortable and very contagious, cause
congenital defects, or carcinogenic.
•Viruses can affect the food supply: crop plants
and food animals.
•The relatively simple nature of viruses makes
them useful as model systems for many of the
basic problems in biology.
Viruses in antiquity: polio
Smallpox: first described in India, 5th century B.C.
Tulip mosaic virus: Variegated tulips first described in 1576
Viruses are small!
Filter systems used to
characterize viruses
Tobacco moasic virus:
Demonstration of infectivity of
ultrafiltrate by Mayer 1886
The pace of early discovery of
new infectious agents
Plants, bacteriophages and
animal viruses: the three
general areas of virology
Advances from plant virology
The ability to isolate large amounts of viruses
from plants permitted extensive chemical and
physical analyses, e.g.:
•The first demonstration that viruses
consisted of proteins and nucleic acids.
•The crystallization of TMV by Stanley
(1935) was a paradigm shift in that it
demonstrated that agents able to reproduce
in living cells could also behave like
macromolecules.
Bacteriophage
· Initial focus on the hypothesis of bacteriophage as antibacterial
therapies.
· Although this proved to be untenable, this work set the
technological foundation for molecular biology as we know it.
Examples include:
· Discovery that nucleic acids are the molecules of genetic
inheritance (Hershey & Chase 1952, also credit Oswald, MacLeod
and McCarthy, 1944),
· The first model systems for DNA replication (M13),
· Control of gene expression and recombination (λ),
· Discovery of mRNA
· Elucidation of the factors that control initiation and termination of
both transcription and translation of genetic information,
· Discovery of restriction endonucleases.
Animal virus research
·Pathogenesis of viral infections and
·Epidemiology.
·The need to study animal viruses spurred the
development of techniques for growing animal
cells in vitro.
·Animal virus systems also played a large role in
the development of immunology.
The “New” Molecular Biology is
founded on Virology.
Understanding of cellular functions e.g.:
•DNA replication and repair (SV40),
•RNA splicing (adenoviruses),
•Translation (picornaviruses, poli),
•Protein-protein interactions,
•Gene expression (retroviruses),
•Cancer and malignancy.
•Oncogenes originally discovered in retroviruses.
•Therapeutics: Vectors to introduce foreign genes into
bacteria (insulin) or animals (gene therapy and vaccine
development.
•Commonly used vectors are based on poxviruses,
retroviruses, adenoviruses (among others).
•A particular vector may be able to home
in on
particular cell types (ex. Adenovirus-respiratory tract
cells, retrovirus-mmune system cells)
•others may be more general
The Origin of Viruses
Three possible origins:
1. Products of regressive evolution from
free living cells. Best candidate are
the Poxviruses.
2. Derived from cellular genetic material
that has acquired the capacity to exist
and function independently.
3. Leftovers from the pre-biotic RNA
world.
Definition of a Virus.
• A genetic element containing either RNA or DNA that
is able to alternate between intra- and extracellular
states, the latter being the infectious state.
• Viruses are obligate intracellular parasites. They are
absolutely dependent on the host cells’ synthetic and
energy-yielding apparatus.
• Viruses consist of a nucleic acid genome that is
protected by a protein component (typically
surrounded by a protein shell called a nucleocapsid).
Frequently, there is a second outer shell composed of
lipids and proteins.
Virus characteristics
• A virus is an infectious agent and obligate
intracellular parasite.
• Virus infectious cycle includes a phase in which the
agent consists of a virion. The virion consists of RNA
or DNA coated with one or more proteins (capsid
structure) which is sometimes coated with a
membrane containing lipid and glycoproteins.
• A virus can initiate another infection when
transferred to a suitable host.
• A virus carries genetic information in the form of
RNA or DNA. This genomic nucleic acid carries
information which redirects the genetic and
metabolic apparatus of the infected cell to produce
virions
Terms
• Virion- Morphologically complete (mature)
infectious virus particle.
• Pathogen- Biological disease agent.
• Bacteriophage- Viruses that infect bacteria.
Phage is Greek for eating, since bacteriophage
produced hole on lawns of bacteria.
• Virulence- the ability of an infectious agent to
produce disease. Many viruses are virulent
sometimes and asymtomatic at other times.
The common tasks faced by (almost) all viruses.
1.
2.
3.
4.
5.
6.
7.
8.
Cell attachment – binding to a cell
surface receptor.
Entry via receptor—mediated
endocytosis.
Release of genome into cytoplasm
via membrane fusion.
Transcription of viral mRNAs and
of new viral genomes (RNA viruses)
Viral protein synthesis and
assembly of provirus.
Maturation of viral particle.
Release of virus from cell.
Evasion of host defense and
transmission to new host.
Effects on Host Cells
• Inhibition of Host Macromolecular
Biosynthesis.
• Changes in Regulation of Host Gene
Expression.
• Appearance of New Antigenic Determinants
on the Cell Surface.
• Cell Fusion.
a) HIV-1 infected T-cell
b) Cytoplasm surrounding
multiply nucleated
syncytium