VIRAL DEFINITION AND HISTORY
Claude MUVUNYI M.D., Ph.D.
What are viruses ?
Viruses are distinct from living organisms.
The simplest definition of viruses is
• Submicroscopic
• Obligate intracellular parasites
What are viruses ?
 Viruses are smaller than bacteria, they range in size between
20-300 nanometer ( nm ).
 Viruses contain only one type of nucleic acid, either DNA or
RNA, but never both.
 Viruses consist of nucleic acid surrounded by a protein coat.
Some viruses have additional lipoprotein envelope.
 Viruses lack cellular organelles, such as mitochondria and
ribosomes.
What are viruses ?
 Viruses are obligate cellular parasites. They replicate
only inside living cells.
 Viruses replicate through replication of their nucleic
acid and synthesis of the viral protein.
 Viruses do not multiply in chemically defined media.
 Viruses do not undergo binary fission.
 Viruses are absolutely dependent on the host cell for
their function
What are viruses ?
Definition of a Virus
Sub microscopic entity consisting
of a single nucleic acid surrounded
by a protein coat and capable of
replication only within the living
cells of bacteria, animals or
plants.
Are viruses alive or not ?
 Are viruses alive or not ?
• Inside the host cell, viruses are alive
• Outside, viruses are merely complex assemblages of
metabolically inert chemicals
Virus-related entities
Viroid
• are very small (200-400 bases) circular RNA molecules
with a rod-like secondary structure
• They have no capsid or envelope and are associated
with certain plant diseases
• Their replication strategy is like that of viruses --> they
are obligate intracellular parasites
Virus-related entities
Virusoids
• Are satellite, viroid-like molecules somewhat larger
than viroids (approximately 1000 nucleotides)
• Are dependent on the presence of virus replication
for multiplication
• They are packaged into virus capsids as passengers
Virus-related entities
 Prions
• Are infectious agents consisting of a single type of protein
molecule
• The prion protein and the gene encoding it are also found
in normal 'uninfected' cells
• These agents are associated with Creutzfeldt-Jakob
disease and kuru disease in humans, scrapie in sheep and
bovine spongiform encephalopathy (BSE) in cattle
History of Virology
History of Virology
In 3700BC:
• 1st written record of a virus infection consists of a heiroglyph from
ancient Egypt,
• Typical clinical signs of paralytic poliomyelitis.
History of Virology
In 1196BC: Pharaoh Ramses V, who died, is believed to have
succumbed to smallpox - compare the pustular lesions on the face
of the mummy & those of more recent patients.
History of Virology
 In 1000BC: Smallpox was endemic in China .
• In response, the practice of variolation was developed.
• Recognizing that survivors of smallpox outbreaks were
protected from subsequent infection,
• variolation involved inhalation of the dried crusts from
smallpox lesions like snuff
History of Virology
On 14th May 1796:
Edward Jenner used cowpox-infected material obtained from the
hand of Sarah Nemes, a milkmaid from his home village of Berkley in
Gloucestershire to successfully vaccinate 8 year old James Phipps.
On 1st July 1796, Jenner challenged the boy by deliberately
inoculating him with material from a real case of smallpox !
He did not become infected !!!
History of Virology
History of Virology
However, it was not until Robert Koch & Louis
Pasteur jointly proposed the 'germ theory' of
disease in the 1880s that the significance of
these organisms became apparent.
Robert Koch (1843-1910)
Louis Pasteur (1822-1895)
Koch defined the four famous criteria now known as Koch's postulates
which are still generally regarded as the proof that an infectious agent
is responsible for a specific disease:
Koch's postulates
i.
The agent must be present in every case of the disease.
ii.
The agent must be isolated from the host & grown in vitro.
iii.
The disease must be reproduced when a pure culture of the agent is inoculated into a healthy
susceptible host.
iv.
The same agent must be recovered once again from the experimentally infected host.
History of Virology
In 1885: Louis Pasteur Subsequently, worked extensively on
rabies, which he identified as being caused by a 'virus' (from the
Latin for 'poison')
in spite of this, he did not discriminate between bacterial & other
agents of disease.
History of Virology
In 1892: Dmiti Iwanowski (1864-1920) described the first
"filterable" infectious agent - tobacco mosaic virus (TMV) - smaller
than any known bacteria.
Iwanowski was the first person to discriminate between viruses and
other infectious agents, although he was not fully aware of the
significance of this finding.
This is generally recognized as the
beginning of Virology
History of Virology
In 1898: Martinus Beijerinick (1851-1931) extended Iwanowski's
work with TMV and formed the first clear concept of the virus
"contagium vivum fluidum" - soluble living germ.
Beijerinick confirmed and extended Iwanowski's work and was the
person who developed the concept of the virus as a distinct entity.
History of Virology
Also in 1898: Freidrich Loeffler (1852-1915) and Paul Frosch (18601928) demonstrated that foot and mouth disease is caused by such
"filterable" agents.
Loeffler and Frosch were the first to prove that viruses could infect
animals as well as plants.
History of Virology
 In 1900: Walter Reed (1851-1902) confirmed that yellow
fever is spread by mosquitoes. Although Reed did not
dwell on the nature of the yellow fever agent, he and his
coworkers were the first to show that viruses could be
spread by insect vectors such as mosquitoes.
 Dr. Carlos Finlay (Cuba) did the discovery of the yellow
fever vector.
Walter Reed (1851-1902)
History of Virology
 In 1908: Karl Landsteiner (1868-1943) and Erwin
Popper proved that poliomyelitis was caused by
a virus.
 Landsteiner and Popper were the first to prove
that viruses could infect humans as well as
animals.
Karl Landsteiner 1868 – 1943
(Nobel Prize, 1930).
History of Virology
 In 1911: Francis Peyton Rous (1879-1970)
demonstrated that a virus (Rous sarcoma virus) can
cause cancer in chickens
 Rous was the first person to show that a virus could
cause cancer.
Francis Peyton Rous (1879-1970)
(Nobel Prize, 1966).
History of Virology
 In 1915: Frederick Twort (1877-1950) discovered viruses infecting
bacteria.
 In 1917: Felix d'Herelle (1873-1949) independently discovered viruses of
bacteria and coins the term bacteriophage. The discovery of
bacteriophages provided an invaluable opportunity to study virus
replication at a time prior to the development of tissue culture when the
only way to study viruses was by infecting whole organisms.
Frederick Twort (1877-1950)
Felix d'Herelle (1873-1949)
History of Virology
In 1933: Isolation of human influenza virus
• Transfer from animals to humans 6000 years ago
• Pandemics 1918 (Spanish flu, H1N1), 1957 (Asian,
H2N2), 1968 (Hong Kong, H1N2), 2009 (Mexican,
H1N1).
• Influenza A virus infects chicken embryos
• Production of virus
• Production of influenza vaccines
History of Virology
 In 1938: Max Theiler (1899-1972) developed a liveattenuated vaccine against yellow fever
• Theiler's vaccine was so safe and effective that it is still in use
today!
• This work saved millions of lives and set the model for the
production of many subsequent vaccines.
(Nobel Prize, 1951).
History of Virology
 In 1939: Emory Ellis (1906-) and Max Delbruck
(1906-1981) established the concept of the "one
step virus growth cycle" essential to the
understanding of virus replication (Nobel Prize,
1969).
 This work laid the basis for the understanding of
virus replication - that virus particles do not
"grow" but are instead assembled from
preformed components.
History of Virology
In 1940: Helmuth Ruska (1908-1973) used an
electron microscope to take the first pictures
of virus particles.
Along with other physical studies of viruses,
direct visualization of virions was an important
advance in understanding virus structure.
History of Virology
 In 1949: John Enders (1897-1985), Thomas Weller
(1915-) and Frederick Robbins (1916-) were able to
grow poliovirus in vitro using human tissue culture
(Nobel Prize, 1954).
 This development led to the isolation of many new
viruses in tissue culture.
John Enders (1897-1985),
History of Virology
In 1957: Carleton Gajdusek proposes that a
"slow virus" is responsible for the prion
disease kuru (Nobel Prize, 1976).
Gajdusek showed that the course of the kuru
is similar to that of scrapie, that kuru can be
transmitted to chimpanzees and that the
agent responsible is an atypical virus.
History of Virology
 In 1963: Baruch Blumberg discovered hepatitis B virus
(HBV) (Nobel Prize, 1976).
 Blumberg went on to develop the first vaccine against the
HBV, considered by some to be the first vaccine against
cancer because of the strong association of hepatitis B with
liver cancer.
Baruch Blumberg (1925 – 2011)
History of Virology
 In 1967: Theodor Diener discovered viroids, agents of
plant disease which have no protein capsid.
 Viroids are infectious agent consisting of a low
molecular weight RNA that contains no protein capsid
responsible for many plant diseases.
History of Virology
 In 1970: Howard Temin (1934-1994) and David
Baltimore independently discovered reverse
transcriptase in retroviruses (Nobel Prize, 1975).
 The discovery of reverse transcription established a
pathway for genetic information flow from RNA to DNA,
refuting the so-call "central dogma“ of molecular
biology.
History of Virology
In 1977: Richard Roberts, and independently
Phillip Sharp, show that adenovirus genes are
interspersed with non-coding segments that
do not specify protein structure (introns)
(Nobel Prize, 1993).
The discovery of gene splicing in adenovirus
was subsequently found to apply to cellular
genes – a fundamental principle.
History of Virology
 In 1979: Smallpox was officially declared to be
eradicated by the World Health Organization (WHO).
 The last naturally occurring case of smallpox was seen
in Somalia in 1977. This was the first microbial disease
ever to be completely eliminated.
History of Virology
In 1981: Yorio Hinuma and colleagues isolated
human T-cell leukaemia virus (HTLV) from the
patients with adult T-cell leukaemia.
Although several viruses are associated with
human tumours, HTLV was the first
unequivocal human cancer virus to be
identified.
History of Virology
 In 1982: Stanley Prusiner demonstrates that
prions are infectious proteins.
 Prions cause scrapie, a fatal neurodegenerative
disease of sheep (Nobel Prize, 1997).
 This was the most significant advance in
understanding of what were previously called
"slow virus" diseases and are now known as
transmissible spongiform encepthalopathies
(TSEs).
History of Virology
In 1983: Luc Montaigner (Nobel prize, 2008)
and Robert Gallo announced the discovery of
human immunodeficiency virus (HIV), the
causative agent of AIDS.
In only 2-3 years since the start of the AIDS
epidemic the agent responsible was identified.
History of Virology
In 1989: Hepatitis C virus (HCV), the source of
most cases of nonA, nonB hepatitis, was
definitively identified.
This was the first infectious agent to be
identified by molecular cloning of the
genome rather than by more traditional
techniques (see 1994).