WHAT IS A VIRUS?
Viruses may be defined as acellular organisms
whose genomes consist of nucleic acid, and
which obligately replicate inside host cells using
host metabolic machinery to different extents, to
form a pool of components which assemble into
particles called virions.
F Viruses cannot be
grown on sterile media,
but require the presence
of specific host cells.
F A virus differs from a cell in three fundamental ways:
i
A virus usually has only a single type of nucleic acid serving as its
genetic material. This can be single or double stranded DNA or RNA;
ii Viruses contain no enzymes of energy metabolism, thus cannot
make ATP;
iii Viruses do not encode sufficient enzymatic machinery to synthesize
their component macromolecules, specifically, no protein synthesis
machinery.
Fundamentally then, a virus is:
A package of genetic information protected
by a protein shell for delivery into a host cell
to be expressed and replicated
Viruses are distinguished from other obligate parasites, some of
which are even simpler than viruses:
MYCOPLASMA: Small bacterium that grows only in complex medium or attached to eucaryotic cells.
CHLAMYDIA: Obligate intracellular bacterial parasite which depends on eucaryotic cell for energy.
PROTOZOA: Obligate intracellular parasite that replicate within eucaryotic cells.
VIROID: Infectious agents of plants that exist as naked nucleic acid (circular single stranded (ss) ssRNA).
HEPATITIS DELTA VIRUS (HDV): Viroid-like agent whose replication is dependent upon HBV.
PRION (proteinacious infectious agent): Hypothesized identity of the
unconventional slow viruses (such as the Kuru, Scrapie and “Mad cow” disease
agents). No nucleic acid is known to be required for prion function. They are
thought by many to consist solely of protein and perhaps lipids. Study of these
agents has resulted in 2 nobel prize awards.
Kuru
Scrapie
BSE
vCJD
BSE
in
Britian
80
70
CJD,
nvCJD
in
Britian
60
50
40
30
20
10
0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
Recognition of viruses
F How long viruses have been within our midst?
1500 BC: Leg deformities indicative of poliomyelitis, pock marks indicative of smallpox and.
"Virus" is from the Greek
meaning for "poison" and
was initially described by
Edward Jenner in 1798.
During the 1800's, all infectious agents were considered to be viruses until Koch developed pure culture techniques
which allowed the separation and growth of bacteria. In the late 1800's: Bacteria were purified and established as
disease causing agents. It then became possible to distinguish them from the "filterable agents", those able to pass
through special filters designed to prevent the passage of bacteria. The first viruses described were foot and mouth
disease (a picornavirus), 1898, Yellow fever (a flavivirus), 1900, Rous sarcoma virus (an oncogenic retrovirus), 1906.
Viral diseases have played a major role in human history
over whatever time scale we choose to explore:
Over the past 1000 years: Smallpox and measles were brought to North and South
America by early European explorers/conquerers. These diseases, for which the
native American populations had no acquired partial immunity, killed large fractions
of the populations, and were a major factor in the decimation of these societies.
Over the past 100 years: A newly emerged strain of
influenza killed 20 million people in 1918-1919 in the
immediate aftermath of World War I. A decade later,
polio became one of the most feared infections of
children and young adults (including Franklin D.
Roosevelt, the U.S. President throughout the Depression
and World War II).
As the century entered its final 20 years, a new
~100% lethal virus, HIV, spread rapidly around the
world via body fluid transmission.
Over the past 10 years: As the global HIV epidemic continues, sporadic cases and
outbreaks in humans of some non-human host viruses such as Ebola and Hanta raise
the concern about future epidemics by other viruses in the new century.
FourCorners Virus (Hanta)
THE DISCIPLINE OF VIROLOGY
The study of virology inherently involves a merging together of what has traditionally
been thought of as two separate "kinds" of science: basic and applied science. We want to
figure out how viruses are transmitted, how they replicate, and how the host organism
responds. We also want to figure out how to prevent transmission, how to interfere with
virus replicaton, and how to confer immunity on the host. The "applied" follows from, and
is dependent upon, the "basic" in a quite direct way. Virology as it is studied today, is
therefore an outgrowth of both:
Infectious diseases - because of the recognition of
viral pathogens.
Molecular Biology- because of the usefulness of
viruses as probes of cell and molecular biology and
metabolism, and as vectors with strong potential for
gene therapy.
Mouse primary spleen cells transduced with a
GFP (green fluorescent protein)-retrovirus vector
WHERE WE STAND IN 2001:
PREVENTING • CONTROLING • CURING VIRAL DISEASES
Smallpox: effective vaccine; this is the only viral disease that has been wiped out worldwide
Measles: effective vaccine since 1963; this disease could be eliminated with a world-wide effort
Influenza: effective strain-specific vaccine, but new variant strains emerge periodically
Polio: effective vaccine; will soon be the second viral disease wiped out
HIV: no vaccine; effective drugs, but they are costly and toxic, plus resistant strains appear.
World-wide spread continues via intimate contact. 50 million infected thus far
Ebola: no vaccine; important host species unknown (found recently in chimps and rodents);
outbreaks controllable because people die quickly and human-human transmission is via blood
Hanta: no vaccine; rodent host; easy transmission to humans, but outbreaks controllable
We also share the world, and our bodies, with viruses that cause hepatitis, respiratory disease,
mononucleosis, diarrhea, genital warts, genital herpes, and some forms of cancer
How are viruses classified ?
Hierarchical virus classification: (order) family - subfamily - genus - species - strain/type
All families have the suffix viridae, e.g.:
*
*
*
*
Poxviridae
Herpesviridae
Parvoviridae
Retroviridae
Genera have the suffix virus. Within the Picornaviridae there are 5 genera:
*
*
*
*
*
enterovirus (alimentary tract), species e.g. poliovirus 1, 2, 3
cardiovirus (neurotropic), species e.g. mengovirus
rhinovirus (nasopharyngeal region), species e.g. Rhinovirus 1a
apthovirus (cloven footed animals ), species e.g. FMDV-C
hepatovirus (liver), species e.g. Hepatitis A virus
Virus naming and classification
Usually based on data available at the time of discovery:
i
Disease they are associated with, e.g.:
Poxvirus, Hepatitis virus, HIV, measles virus
ii
Cytopathology they cause, e.g.:
Respiratory Syncytial virus, Cytomegalovirus
iii
Site of isolation, e.g.:
Adenovirus, Enterovirus, Rhinovirus
iv
Places discovered or people that
discovered them, e.g.:
Epstein-Barr virus, Rift Valley Fever
v
Biochemical features, e.g.:
Retrovirus, Picornavirus, Hepadnavirus
RSV
These naming conventions can lead to confusion later, e.g.,
viral hepatitis is caused by at least 6 different viruses
“Infectious”
Viral
hepatitis
“Serum”
A
E
F, G,
? Other *
NANB
B
Enterically
transmitted
C
Parenterally
transmitted
D
* 10-20% of cases of presumed viral hepatitis are still not accounted for
Thus,
Different viruses can cause (nearly) the same
symptoms. e.g., the hepatitis viruses
However, different members of the same group
can cause different symptoms. e.g., the herpes
viruses
Herpesviruses

HSV
Herpes Simplex Virus

VZV
CMV
EBV
Varicella Zoster Virus
Cytomegalovirus
Epstein-Barr Virus



and HHV-6, HHV-7, HHV-8…..
(Human HerpesVirus-#)
Cold sores (type 1),
Genital lesions (type 2)
Chicken pox
Mononucleosis
Mononucleosis,
Burkitt’s lymphoma,
Nasopharyngeal carcinoma
Virus Classification is now based principally on analysis of the particle:
Morphology:
by electron microscopy
Serology:
antigenic cross-reactivity
Genetic material:
form of nucleic acid
ssDNA (+ or - strand)
dsDNA
ssRNA (+ or - strand)
dsRNA
segmented RNA
genetic organization
sequence homology
DNA sequence
Hybridization
Rotavirus
Animal virus classification: DNA Viruses
Family
Pox
Genome
<---------------------------------------dsDNA-------------------------------------->
Capsid
symmetry
Complex
Envelope
<-----------------Yes------------------>
e.g.
Vaccinia virus
Molluscum
Contagiosum
Herpes
Adeno
Papova
Parvo
Hepadna
ssDNA
Partial dsDNA
<---------------------------------------------Icosahedral-------------------------------------------------->
Herpes simplex
virus 2
<-----------------------------No------------------------------>
Human
adenovirus
Papilloma
AdenoAssociated
Yes
Hepatitis B
Plus Sense RNA Viruses
Plus-sense RNA viruses
Family
Genome
Corona
Toga/Flavi
Picorna
Calici
<-------------------------------------------ss (+) RNA--------------------------------------------->
Capsid symme try
Helical
Envelope
e.g.
<----------------------Yes-------------------->
Human corona
Rubella virus
virus
Hepatitis C vi rus
Retro
Diploid ( +) RNA
<--------------------------------------Icosahedral------------------------------------------------->
<---------------------No---------------------->
Polio
Norwalk agent
Hepatitis A vi rus
Hepatitis E virus
Yes
HIV-1
Minus Sense RNA Viruses
Minus-sense RNA viruses
Family
Genome
Paramyxo
Rhabd o
Filo
<-----------------ss(-) RNA------------------------>
Capsid
symmetry
Envelope
Orthomyxo
Arena
Bunya
ss(-) RNA
ss(+) or (+/-)
ss(+) or (+/-)
segments
segments
segments
<---------------------------------------------------Helical------------------------------------------------------->
Reo
ds RNA
segments
Icosahedral
<----------------------------------------------------Yes----------------------------------------------------------->
No
Measles
Mu mps
Parainfluenza
Rotavirus
e.g.
Rabies virus
Ebo la virus
Influenza
virus
Lassa virus
Hanta virus