Basic Concept of Virology
These projections
GENERAL PROPERTIES OF VIRUSES
 Terms and definitions in Virology
 Evolutionary origin of Viruses
 Classifications of Viruses
 Principles of Virus Structure
 Chemical Composition of Viruses
 Cultivation and Assay of Viruses
 Laboratory Safety
 Reaction To Physical And Chemical Agents
 Replication Of Viruses
 Natural History (Ecology) And
 Modes Of Transmission Of Viruses
TERMS AND DEFINITIONS IN VIROLOGY
• Viruses
 the smallest infectious agents (about 20 nm
to 300 nm in diameter)
 contain only one kind of nucleic acid (RNA
or DNA) as their genome.
 are inert in the extracellular environment;
they replicate only in living
•Capsid
 The protein shell, or coat, that encloses the
nucleic acid genome.
• Capsomeres
 Morphologic units seen in the electron
microscope on the surface of icosahedral
virus particles . Capsomeres represent
clusters of polypeptides, but the
morphologic units do not necessarily
correspond to the chemically defined
structural units.
• Defective virus
 A virus particle that is functionally deficient
in some aspect of replication.
• Envelope
 A lipid-containing membrane that surrounds
some virus particles. It is acquired during
viral maturation by a budding process
through a cellular membrane. Virus-
encoded glycoproteins are exposed on the
surface of the envelope.
are called peplomers.
• Nucleocapsid
 The protein–nucleic acid complex
representing the packaged form of the viral
genome. The term is commonly used in
cases in which the nucleocapsid is a
substructure of a more complex virus
particle.
• Structural units
 The basic protein building blocks of the
coat. They are usually a collection of more
than one non-identical protein subunit. The
structural unit is often referred to as a
protomer.
• Subunit
 A single folded viral polypeptide chain.
• Virion
 The complete virus particle. In some
instances (eg, papillomaviruses,
picornaviruses), the virion is identical with
the nucleocapsid. In more complex virions
(herpesviruses, orthomyxoviruses), this
includes the nucleocapsid plus a
surrounding envelope. This structure, the
virion, serves to transfer the viral nucleic
acid from one cell to another.
EVOLUTIONARY ORIGIN OF VIRUSES
• The origin of viruses is not known, Two theories
of viral origin can be summarized as follows:
1. Viruses may be derived from DNA or RNA
nucleic acid components of host cells that
became able to replicate autonomously and
evolve independently. They resemble genes
that have acquired the capacity to exist
independently of the cell. Some viral
sequences are related to portions of cellular
genes encoding protein functional domains.
It seems likely that at least some viruses
evolved in this fashion.
2. Viruses may be degenerate forms of
intracellular parasites. There is no evidence
that viruses evolved from bacteria, although
 other obligately intracellular organisms (eg,
rickettsiae and chlamydiae) presumably did
so. However, poxviruses are so large and
complex that they might represent
evolutionary products of some cellular
ancestor.
CLASSIFICATION OF VIRUSES
A. Basis of Classification
The following properties have been used as a
basis for the classification of viruses.
1. Virion morphology: including size, shape,
type of symmetry, presence or absence of
peplomers, and presence or absence of
membranes.
2. Virus genome properties: including type of
nucleic acid (DNA or RNA), size of genome
in kilobases (kb) or kilobase pairs (kbp),
strandedness (single or double), whether
linear or circular, sense (positive, negative,
ambisense),segments (number, size),
nucleotide sequence, G + C content, and
presence of special features
(repetitiveelements, isomerization, 5′-
terminal cap, 5′-terminal covalently linked
protein, 3′- terminal poly(A) tract).
3. Genome organization and replication:
including gene order, number and position
of open reading frames,strategy of
replication (patterns of transcription,
translation), and cellular sites (accumulation
of proteins, virion assembly, virion release).
4. Virus protein properties: including
number, size, and functional activities of
structural and nonstructural proteins, amino
acid sequence, modifications (glycosylation,
phosphorylation, myristylation), and special
functional activities (transcriptase, reverse
transcriptase, neuraminidase, fusion
activities).
5. Antigenic properties.
6. Physicochemical properties of the virion:
including molecular mass, buoyant density,
pH stability, thermal stability, and
susceptibility to physical and chemical
agents, especially ether and detergents.
7. Biologic properties: including natural host
range, mode of transmission, vector
relationships, pathogenicity, tissue tropisms,
and pathology.
B. Universal System of Virus Taxonomy
 A system has been established in which
viruses are separated into major groupings
—called families—on the basis of virion
morphology, genome structure, and
strategies of replication. Virus family names
have the suffix -viridae.
 Within each family, subdivisions called
genera are usually based on biological,
genomic, physicochemical, or serologic
differences. Criteria used to define genera
vary from family to family. Genus names
carry the suffix -virus. In several families
(Herpesviridae, Paramyxoviridae,
Parvoviridae, Poxviridae, Reoviridae,
Retroviridae), a larger grouping called
subfamilies has been defined, reflecting the
complexity of relationships among member
viruses. Virus orders may be used to group
virus families that share common
characteristics. For example, order
Mononegavirales encompasses the
Bornaviridae, Filoviridae, Paramyxoviridae,
and Rhabdoviridae families.
 By 2000, the International Committee on
Taxonomy of Viruses had organized more
than 4000 animal and plant viruses into 56
families and 233 genera, with hundreds of
viruses still unassigned.
 Of these, 24 families contained viruses that
infect humans and animals.
C. Survey of DNA-Containing Viruses
A. Parvoviruses
B. Anelloviruses
C. Polyomaviruses
D. Papillomaviruses
E. Adenoviruses
F. Hepadnaviruses
G. Herpesviruses
H. Poxviruses
A. PARVOVIRUSES
 are very small viruses with a particle size of
about 18–26 nm.
  cubic symmetry, with 32 capsomeres, no
envelope.
 The genome is linear, single-stranded DNA,
5.6 kb in size.
 Replication occurs only in actively dividing
cells; capsid assembly takes place in the
D. PAPILLOMAVIRUSES
nucleus of the infected cell.
 Many parvoviruses replicate autonomously,
but the adenoassociated satellite viruses
are defective, requiring the presence of an
adenovirus or herpesvirus as “helper.”
 Human parvovirus B19 replicates in
immature erythroid cells and causes several
adverse consequences, including aplastic
crisis, fifth disease, and fetal death.
B. ANELLOVIRUSES
 are small (~30 nm in diameter)
 icosahedral virions that lack an envelope.
E. ADENOVIRUSES
 The viral genome is circular, single-stranded
DNA, 2.0–3.9 kb in size.
 The genome is negative sense. -include the
torque teno viruses.
 globally distributed in the human population
and are also found in many animal species.
No specific disease associations have been
proven. There is limited knowledge about
viral gene expression and replication.
C. POLYOMAVIRUSES
 are small (45 nm)
 nonenveloped, heat-stable, ether-resistant
viruses exhibiting cubic symmetry, with 72
capsomeres.
 The genome is circular, double-stranded
DNA,5 kbp in size.
 These agents have a slow growth cycle,
stimulate cell DNA synthesis, and replicate
within the nucleus.
 The most well-known human
polyomaviruses are JC virus, the causative
agent of progressive multifocal
leukoencephalopathy; BK virus, associated
with nephropathy in transplant recipients;
and Merkel cell virus, found associated with
the majority of Merkel cell skin carcinomas.
SV40, a primate virus, can also infect
humans.
 Most animal species harbor one or more
polyomaviruses. They produce chronic
infections in their natural hosts, and most
mammalian viruses can induce tumors in
some animal species.
 similar to polyomaviruses in some respects
but with a larger genome (8 kbp) and
particle size (55 nm).
 There are many genotypes of human
papillomaviruses, also k nown as “wart”
viruses; certain types are causative agents
of genital cancers in humans.
 are very host and tissue specific and cannot
be grown in cultured cells in vitro.
 Many animal species carry
papillomaviruses.
 Adenoviruses are medium-sized (70–90
nm)
 nonenveloped viruses exhibiting cubic
symmetry, with 252 capsomeres.
 Fibers protrude from the vertex
capsomeres.
 The genome is linear, double-stranded
DNA, 26–45 kbp in size.
 Replication occurs in the nucleus.
 Complex splicing patterns produce mRNAs.
 At least 51 types infect humans, especially
in mucous membranes, and some types can
persist in lymphoid tissue.
 Some adenoviruses cause acute respiratory
diseases, conjunctivitis, and gastroenteritis.
Some human adenoviruses can induce
tumors in newborn hamsters. Many
serotypes infect animals.
F. HEPADNAVIRUSES
 Hepadnaviruses are small (40–48 nm)
viruses -containing circular double-
stranded DNA molecules that are 3.2
kbp in size.
 The viral DNA in the particles contains a
large single-stranded gap.
 Replication involves repair of the single-
stranded gap in the DNA, transcription
 of RNA, and reverse transcription of the  The genome is linear, covalently closed,
RNA to make genomic DNA. double-stranded DNA, 130–375 kbp in size.
 The virus consists of a 27-nm  Poxvirus particles contain about 100
icosahedral nucleocapsid core within a proteins, including many with enzymatic
closely adherent envelope that contains activities, such as a DNA-dependent RNA
lipid and the viral surface antigen. polymerase.
 The surface protein is characteristically  Replication occurs entirely within the cell
overproduced during replication of the cytoplasm.
virus, which takes place in the liver, and  All poxviruses tend to produce skin lesions.
is shed into the bloodstream. Some are pathogenic for humans
 cause acute and chronic hepatitis; (smallpox,vaccinia, molluscum
persistent infections are associated with contagiosum); others that are pathogenic for
a high risk of developing liver cancer. animals can infect humans (cowpox,
 Viral types are known that infect monkeypox).
mammals and ducks.
D. Survey of RNA-Containing Viruses
G. HERPESVIRUSES
A. Picornaviruses
 a large family of viruses 150–200 nm in B. Astroviruses
diameter. C. Caliciviruses
 The nucleocapsid is 100 nm in diameter, D. Hepeviruses
with cubic symmetry and 162 capsomeres, E. Picobirnaviruses
surrounded by a lipid-containing envelope. F. Reoviruses
 The genome is linear, double-stranded G. Arboviruses and Rodent-Borne Viruses
DNA, 125–240 kbp in size. H. Togaviruses
 The presence of terminal and internal I. Flaviviruses
reiterated sequences results in several J. Arenaviruses
isomeric forms of genomic DNA. K. Coronaviruses
 Virions contain more than 30 proteins. L. Retroviruses
 Latent infections may last for the life span of M. Orthomyxoviruses
the host, usually in ganglial or N. Bunyaviruses
lymphoblastoid cells. O. Bornaviruses
P. Rhabdoviruses
 Human herpesviruses include herpes
Q. Paramyxoviruses
simplex types 1 and 2 (oral and genital
R. Filoviruses
lesions), varicella- zoster virus (chickenpox
S. Other Viruses
and shingles), c ytomegalovirus, Epstein-
Barr virus (infectious mononucleosis and
A. PICORNAVIRUSES
association with human neoplasms), human
- Picornaviruses are small (28–30 nm)
herpesviruses 6 and 7 (T l ymphotropic),
- ether-resistant viruses exhibiting cubic
and human herpesvirus 8 (associated
symmetry.
withKaposi sarcoma).
- The RNA genome is single stranded and
 Other herpesviruses occur in many animals.
positive sense (ie, it can serve as an
H. POXVIRUSES mRNA) and is 7.2–8.4 kb in size.
- The groups infecting humans are
 are large brick-shaped or ovoid viruses enteroviruses (polioviruses,
220–450 nm long × 140– 260 nm wide × coxsackieviruses, echoviruses, and
140–260 nm thick. rhinoviruses [more than 100 serotypes
 The particle structure is complex, with a causing common colds]) and
lipid-containing envelope. hepatovirus (hepatitis A)
 - Rhinoviruses are acid labile and have a
high density; other enteroviruses are
acid stable and have a lower density.
- Picornaviruses infecting animals include
foot-and-mouth disease of cattle and
encephalomyocarditis of rodents.
B. ASTROVIRUSES
- similar in size to picornaviruses (28–30
nm),
- particles display a distinctive star-
shaped outline on their surfaces
- The genome is linear, positive-sense,
single-stranded RNA, 6.4–7.4 kb in size.
- These agents may be associated with
gastroenteritis in humans and animals
C. CALICIVIRUSES
- are similar to picornaviruses but slightly
larger (27–40 nm)
- The particles appear to have cup-
shaped depressions on their surfaces
- The genome is single-stranded, positive-
sense RNA, 7.4–8.3 kb in size; the virion
has no envelope
- Important human pathogens are the
noroviruses (eg, Norwalk virus), the
cause of epidemic acute gastroenteritis.
- Other agents infect cats and sea lions
as well as primates
D. HERPESVIRUSES
- similar to caliciviruses. The particles are
small (27–34 nm) and ether resistant.
- The genome is single-stranded, positive-
sense RNA, 7.2 kb in size.
- It lacks a genome-linked protein (VPg).
- Human hepatitis E virus belongs to this
group.
E. PICOBIRNAVIRUSES
- are small (35–40 nm)
- non-enveloped viruses with icosahedral
structure.
- The genome is linear, double-stranded,
segmented (bipartite) RNA (2
segments), total in 4.0–4.5 kb
F. REOVIRUSES
- are medium-sized (60–80 nm),
- ether-resistant, nonenveloped viruses
having icosahedral symmetry.
- Particles have two or three protein shells
with channels extending from the
surface to the core; short spikes extend
from the virion surface.
- The genome is linear, double-stranded,
segmented RNA (10–12 segments),
totaling 16–27 kbp in size.
- Individual RNA segments range in size
from 680 bp to 3900 bp.
- Replication occurs in the cytoplasm;
genome segment reassortment occurs
readily.
- Reoviruses of humans include
rotaviruses, which have a distinctive
wheel-shaped appearance and
cause gastroenteritis.
- Antigenically similar reoviruses infect
many animals.
- The genus Coltivirus includes Colorado
tick fever virus of humans.
G. ARBOVIRUSES AND RODENT-BORNE
VIRUSES
- are ecologic groupings (not a virus
family) of viruses with diverse physical
and chemical properties.
- The arboviruses (there are more than
350 of them) have a complex cycle
involving arthropods as vectors that
transmit the viruses to vertebrate hosts
by their bite.
- Viral replication does not seem to harm
the infected arthropod
- Arboviruses infect humans, mammals,
birds, and snakes and use mosquitoes
and ticks as vectors.
- Human pathogens include dengue,
yellow fever, West Nile fever, and
encephalitis viruses.
- Rodent-borne viruses establish
persistent infections in rodents and are
transmitted without an arthropod vector.
- Human diseases include hantavirus
infections and Lassa fever
- The viruses in these ecologic groupings
belong to several virus families,
including arenavirus, bunyavirus,
flavivirus, reovirus, rhabdovirus, and
togavirus

H. TOGAVIRUSES
- Many arboviruses that are major human
pathogens, called alphaviruses—as well
as rubella virus—belong to this group.
- They have a lipid-containing envelope
and are ether sensitive, and their
genome is single-stranded, positive-
sense RNA, 9.7–11.8 kb in size.
- The enveloped virion measures 70 nm.
The virus particles mature by budding
from host cell membranes.
- An example is eastern equine
encephalitis virus. Rubella
virus has no arthropod vector
I. FLAVIVIRUSES
- are enveloped viruses, 40–60 nm in
diameter, containing single- stranded,
positive-sense RNA.
- Genome sizes vary from 9.5 kb
(hepatitis C) to 11 kb (flaviviruses) to
12.5 kb (pestiviruses)
- Mature virions accumulate within
cisternae of the endoplasmic reticulum.
This group of arboviruses includes
yellow fever virus and dengue viruses.
Most members are transmitted by blood-
sucking arthropods. Hepatitis C virus
has no known vector
J. ARENAVIRUSES
- are pleomorphic, enveloped viruses
ranging in size from 50 nm to 300 nm
(mean, 110–130 nm).
- The genome is segmented, circular,
single-stranded RNA
- is negative sense and ambisense, 10–
14 kb in total size
- Replication occurs in the cytoplasm with
assembly via budding on the plasma
membrane.
- The virions incorporate host cell
ribosomes during maturation, which
gives the particles a “sandy” appearance
- Most members of this family are unique
to tropical America (ie, the Tacaribe
complex).
- All arenaviruses pathogenic for humans
cause chronic infections in rodents
- Lassa fever virus of Africa is one
example. These viruses require
maximum containment conditions in the
laboratory.
K. CORONAVIRUSES
- Coronaviruses are enveloped 120- to
160-nm particles containing an
unsegmented genome of positive-sense,
single-stranded RNA, 27–32 kb in size;
the nucleocapsid is helical,9–11 nm in
diameter.
- Coronaviruses resemble
orthomyxoviruses but have petal-shaped
surface projections arranged in a fringe,
similar to a solar corona.
- Coronavirus nucleocapsids develop in
the cytoplasm and mature by budding
into cytoplasmic vesicles. These viruses
have narrow host ranges.
- Most human coronaviruses cause mild
acute upper respiratory tract illnesses
—“colds”—but a new coronavirus
identified in 2003 causes a severe
acute respiratory syndrome (SARS).
- Toroviruses, which cause
gastroenteritis, form a distinct genus.
Coronaviruses of animals readily
establish persistent infections and
include mouse hepatitis virus and avian
infectious bronchitis virus.
L. RETROVIRUSES
- are spherical, enveloped viruses (80–
110 nm in diameter)
- genome contains two copies of linear,
positive-sense, single-stranded RNA of
the same polarity as viral mRNA.
- Each monomer RNA is 7–11 kb in size.
Particles contain a helical nucleocapsid
within an icosahedral capsid. Replication
is unique; the virion contains a
reverse transcrip-tase enzyme that
produces a DNA copy of the RNA
genome.
- This DNA becomes circularized and
integrated into host chromosomal DNA.
The virus is then replicated from the
integrated “provirus” DNA copy.
- Virion assembly occurs by budding on
plasma membranes.
- Hosts remain chronically infected.
 - are widely distributed; there are also
endogenous proviruses resulting from
ancient infections of germ cells
transmitted as inherited genes in most
species.
- Leukemia and sarcoma viruses of
animals and humans, foamy viruses of
primates, and lentiviruses (human
immuno-deficiency viruses; visna of
sheep) are included in this group.
Retroviruses cause acquired immuno-
deficiency syndrome (AIDS) and make
possible the identification of cellular
oncogenes
M. ORTHOMYXOVIRUSES
- are medium-sized, 80- to 120-nm
enveloped viruses exhibiting helical
symmetry.
- Particles are either round or filamentous,
with surface projections that contain
hemagglutinin or neuraminidase activity.
- The genome is linear, segmented,
negative-sense, single-stranded RNA,
totaling 10–13.6 kb in size.
- Segments range from 900 to 2350
nucleotides each.
- The internal nucleoprotein helix
measures 9–15 nm.
- During replication, the nucleocapsid is
assembled in the nucleus; the
hemagglutinin and neuraminidase
accumulate in the cytoplasm. The virus
matures by budding at the cell
membrane.
- All orthomyxoviruses are influenza
viruses that infect humans or animals.
- The segmented nature of the viral
genome permits ready genetic
reassortment when two influenza
viruses infect the same cell, presumably
fostering the high rate of natural
variation among influenza viruses.
- Transmission from other species is
thought to explain the emergence of
new human pandemic strains of
influenza Aviruses.
N. BUNYAVIRUSES
- are spherical or pleomorphic, 80- to 120-
nm enveloped particles.
- The genome is made up of a triple-
segmented, circular, single-stranded,
negative-sense or ambisense RNA, 11–
19 kb in overall size.
- Virion particles contain three circular,
helically symmetric nucleocapsids about
2.5 nm in diameter and 200–3000 nm in
length.
- Replication occurs in the cytoplasm, and
an envelope is acquired by budding into
the Golgi. The majority of these viruses
are transmitted to vertebrates by
arthropods (arboviruses).
- Hantaviruses are transmitted not by
arthropods but by persistently infected
rodents via aerosols of contaminated
excreta.
- They cause hemorrhagic fevers and
nephropathy as well as a severe
pulmonary syndrome.
O. BORNAVIRUSES
- are enveloped, spherical (80–125 nm)
viruses.
- The genome is linear, single-stranded,
nonsegmented, negative-sense RNA,
8.5–10.5 kb in size.
- Unique among nonsegmented,
negative-sense RNA viruses, replication
and transcription of the viral genome
occur in the nucleus.
- Borna disease virus is neurotropic in
animals; a postulated association with
neuropsychiatric disorders of humans is
unproved
P. RHABDOVIRUSES
- are enveloped virions resembling a
bullet, flat at one end and round at the
other, measuring about 75 × 180 nm.
- The envelope has 10-nm spikes.
- The genome is linear, single-stranded,
nonsegmented, negative-sense RNA,
13–16kb in size.
- Particles are formed by budding from
the cell membrane.
- Viruses have broad host ranges.
- Rabies virus is a member of this group.
Q. PARAMYXOVIRUSES
 - are similar to but larger (150–300 nm)
than orthomyxoviruses
- Particles are pleomorphic.
- The internal nucleocapsid measures 13–
18 nm, and the linear,
single-stranded, nonsegmented,
negative-sense RNA is 16–20 kb
in size.
- Both the nucleocapsid and the
hemagglutinin are formed in the
cytoplasm.
- Those infecting humans include mumps,
measles, parainfluenza, metapneumo,
and respiratory syncytial viruses.
- These viruses have narrow host ranges.
In contrast to influenza viruses,
paramyxoviruses are genetically stable.
R. FILOVIRUSES
- are enveloped, pleomorphic viruses that
may appear very long and threadlike.
- They typically are 80 nm wide and about
1000 nm long.
- The envelope contains large peplomers.
- The genome is linear, negative-sense,
single-stranded RNA, 19 kb in size.
Marburg and Ebola viruses cause
severe hemorrhagic fever in Africa.
- These viruses require maximum
containment conditions (Biosafety Level
4) for handling
S. OTHER VIRUSES
- There is insufficient information to permit
classification of
some viruses. This applies to some
viruses of gastroenteritis.
T. VIROIDS
- are small infectious agents that cause
diseases of plants.
- are agents that do not fit the definition of
classic viruses.
- They are nucleic acid molecules without
a protein coat.
- Plant viroids are single-stranded,
covalently closed circular RNA
molecules consisting of about 360
nucleotides and with a highly base-
paired rodlike structure.
- Viroids replicate by an entirely novel
mechanism.
- Viroid RNA does not encode any protein
products; the devastating plant diseases
induced by viroids occur by an unknown
mechanism.
- To date, viroids have been detected only
in plants; none have been demonstrated
to exist in animals or humans.
U. PRIONS
- are infectious particles composed solely
of protein with no detectable nucleic acid
- They are highly resistant to inactivation
by heat, formaldehyde, and ultraviolet
light that inactivate viruses
- The prion protein is encoded by a single
cellular gene. Prion diseases, called
“transmissible spongiform
encephalopathies,” include scrapie in
sheep, mad cow disease in cattle,
and kuru and Creutzfeldt-Jakob disease
in humans. Prions do not appear to be
viruses.
PRINCIPLES OF VIRUS STRUCTURE
 shapes and sizes.
 Structural information is necessary for virus
classification and for establishing structure–
function relationships of viral proteins.
 The particular structural features of each
virus family are determined by the functions
of the virion: morphogenesis and release
from infected cells; transmission to new
hosts; and attachment, penetration, and
uncoating in newly infected cells
 Knowledge of virus structure furthers our
understanding of the mechanisms of certain
processes such as the interaction of virus
particles with cell surface receptors and
neutralizing antibodies. It may lead also to
the rational design of antiviral drugs capable
of blocking viral attachment, uncoating, or
assembly in susceptible cells.
TYPES OF SYMMETRY OF VIRUS PARTICLES
 Electron microscopy, cryoelectron
microscopy, and x-ray diffraction techniques
I. STANDARD ELECTRON MICROSCOPY:
 - The study of viral symmetry
- requires heavy metal stains (eg,
potassium phosphotungstate) to
emphasize surface structure
- resolve fine differences in the basic
morphology of viruses
- The heavy metal permeates the virus
particle like a cloud and brings out the
surface structure of viruses by virtue of
“negative staining”
- The typical level of resolution is 3–4 nm.
- However, conventional methods of
sample preparation often cause
distortions and changes in particle
morphology
II. CRYOELECTRON MICROSCOPY
- uses virus samples quick frozen in
vitreous ice
- fine structural features are preserved,
the use of negative stains is avoided.
- Three-dimensional structural information
can be obtained by the use of computer
image processing procedures.
III. X-RAY CRYSTALLOGRAPHY
- can provide atomic resolution
information, generally at a level of
0.2–0.3 nm.
- specimen must be crystalline, and this
has only been achieved with small,
nonenveloped viruses.
- However, it is possible to obtain high-
resolution structural data on well-defined
substructures prepared from the more
complex viruses.
1. CUBIC SYMMETRY
- icosahedral pattern
- 20 faces (each an equilateral triangle),
12 vertices, and fivefold, threefold, and
twofold axes of rotational symmetry.
- The vertex units have five neighbors
(pentavalent), and all others have six
(hexavalent).
- There are exactly 60 identical subunits
on the surface of an icosahedron.
- Most viruses that have icosahedral
symmetry do not have an icosahedral
shape—rather, the physical appearance
of the particle is spherical.
- Genetic economy requires that a viral
structure be made from many identical
molecules of one or a few proteins
- Viral architecture can be grouped into
three types based on the arrangement
of morphologic subunits:
1. cubic symmetry (eg,
adenoviruses)
2. helical symmetry (eg,
orthomyxoviruses)
3. complex structures (eg,
poxviruses).
2. HELICAL SYMMETRY
- protein subunits are bound in a periodic
way to the viral nucleic acid, winding it
into a helix.
- The filamentous viral nucleic acid–
protein complex (nucleocapsid) is then
coiled inside a lipid-containing envelope.
- Thus, as is not the case with icosahedral
structures, there is a regular, periodic
interaction between capsid protein and
nucleic acid in viruses with helical
symmetry. It is not possible for “empty”
helical particles to form.
- All known examples of animal viruses
with helical symmetry contain RNA
genomes and, with the exception of
rhabdoviruses, have flexible
nucleocapsids that are wound into a ball
inside envelopes
3. COMPLEX STRUCTURES
- Some virus particles do not exhibit
simple cubic or helical symmetry but are
more complicated in structure. For
example, poxviruses are brick shaped,
with ridges on the external surface and a
core and lateral bodies inside.
 
 MEASURING THE SIZES OF VIRUS
- Small size and the ability to pass through
filters that hold back bacteria are classic
attributes of viruses.  (eg, influenza virus hemagglutinin
- However, because some bacteria may be
smaller than the largest viruses, filter ability
is not regarded as a unique feature of
viruses.
- electron microscope
- sedimentation in the ultracentrifuge.
- Direct observation in the electron
microscope is the most widely used method
for estimating particle size.
- Another method that can be used is
sedimentation in the ultracentrifuge. The
relationship between the size and shape of
a particle and its rate of sedimentation
permits determination of particle size.
COMPARATIVE MEASUREMENTS
- Viruses range in diameter from about 20 nm
to 300 nm
- Particles with a twofold difference in
diameter have an eightfold difference in
volume.
- Thus, the mass of a poxvirus is about 1000
times greater than that of the poliovirus
particle, and the mass of a small bacterium
is 50,000 times greater.
- Staphylococcus species have a diameter of
about 1000 nm (1 μm).
- particle size: Pox: 230x400 nm
- polio: 45nm
CHEMICAL COMPOSITION OF VIRUSES
 VIRAL PROTEIN
- major purpose is to facilitate transfer of the
viral nucleic acid from one host cell to
another.
- They serve to protect the viral genome
against inactivation by nucleases,
participate in the attachment of the virus
particle to a susceptible cell, and provide
the structural symmetry of the virus particle.
- determine the antigenic characteristics of
the virus.
- enzymes: (protein)
- Some viruses carry enzymes inside the
virions.
- The structural proteins of viruses have
several important functions.
- The host’s protective immune response is
directed against antigenic determinants of
proteins or glycoproteins exposed on the
surface of the virus particle. Some surface
proteins may also exhibit specific activities
agglutinates red blood cells).
- The enzymes are present in very small
amounts and are probably not important in
the structure of the virus particles; however,
they are essential for the initiation of the
viral replicative cycle when the virion enters
a host cell.
 VIRAL NUCLEIC ACID
-either DNA or RNA 
-The genome may be single or double
stranded, circular or linear, and segmented
or non-segmented. 
- The type of nucleic acid, its strandedness,
and its size are major characteristics used
for classifying viruses into families
 VIRAL LIPID ENVELOPES
- A number of different viruses contain lipid
envelopes as part of their structure.
- Derived from the host cell
- The lipid is acquired when the viral
nucleocapsid buds through a cellular
membrane in the course of maturation.
Budding occurs only at sites where virus-
specific proteins have been inserted into the
host cell membrane. The budding process
varies markedly depending on the replication
strategy of the virus and the structure of the
nucleocapsid. 
- Lipid-containing viruses are sensitive to
treatment with ether and other organic
solvents, indicating that disruption or loss of
lipid results in loss of infectivity.
- Nonlipid-containing viruses are generally
resistant to ether.
Viruses contain a single kind of nucleic acid—either
DNA or RNA—that encodes the genetic information
necessary for replication of the virus.
 VIRAL GLYCOPROTEINS
- Viral envelopes contain glycoproteins
- the envelope glycoproteins are virus
encoded
- The surface glycoproteins of an enveloped
virus attach the virus particle to a target cell
by interacting with a cellular receptor.  1. aerosols—generated by homogenization of
- They are also often involved in the
membrane fusion step of infection.  vibration, or broken glassware;
- The glycoproteins are also important viral
antigens. As a result of their position at the
outer surface of the virion, they are
frequently involved in the interaction of the
virus particle with neutralizing antibody.
CULTIVATION AND ASSAY OF VIRUSES
 Cultivation of Viruses
- cell cultures or in fertile eggs
- Growth of virus in animals is still used for the
primary isolation of certain viruses and for
studies of the pathogenesis of viral diseases
and of viral oncogenesis.
Many viruses can be grown in cell cultures or in
fertile eggs under strictly controlled conditions.
3 BASIC TYPES OF CELL CULTURES:
1. Primary cultures :  7. immunization if relevant vaccines are available.
- made by dispersing cells (usually with
trypsin) from freshly removed host tissues.  Additional precautions and special containment
- they are unable to grow for more than a few
passages in culture.
2. Diploid cell lines: 
- secondary cultures 
- have undergone a change that allows their
limited culture (up to 50 passages) but that
retain their normal chromosome pattern.
3. Continuous cell lines
 cultures capable of more prolonged -
perhaps indefinite-growth that have been
derived from diploid cell lines or from
malignant tissues.
The type of cell culture used for viral cultivation
depends on the sensitivity of the cells to a particular
virus.
LABORATORY SAFETY
Many viruses are human pathogens, and
laboratory-acquired infections can occur.
Laboratory procedures are often potentially
hazardous if proper technique is not followed.
Among the common hazards that might expose
laboratory personnel to the risk of infection are the
following:
 RISK OF INFECTION
infected tissues, centrifugation, ultrasonic
 
2. ingestion—from mouth pipetting, eating or
smoking in the laboratory, or inadequate
washing of hands; 
3. skin penetration—from needle sticks, broken
glassware, hand contamination by leaking
containers, handling of infected tissues, or
animal bites; and
4. splashes into the eye.
 GOOD BIOSAFETY PRACTICES
1. training in and use of aseptic techniques
2. interdiction of mouth pipetting
3. no eating, drinking, or smoking in the laboratory
4. use of personal protective equipment (eg,
coats, gloves, masks) not to be worn outside
the laboratory
5. sterilization of experimental wastes
6. use of biosafety hoods
facilities (Biosafety Level 4) are necessary when
personnel are working with high-risk agents such
as the filoviruses and rabies virus.
REACTION TO PHYSICAL AND CHEMICAL
AGENTS
A. Heat and Cold :
- Icosahedral viruses: losing little infectivity at
37°C for several hours 
- Generally destroyed by heating at 50-60° C
for 30 mins
- Preserved : subfreezing temperatures ;
lyophilization and preserved at dry state at
4°C 
B. Stabilization of Viruses by Salts
- MgCl2, 1 mol/L, stabilizes picornaviruses
and reoviruses; 
- MgSO4, 1 mol/L, stabilizes
orthomyxoviruses and paramyxoviruses
- Na2SO4, 1 mol/L, stabilizes herpesviruses.
C. pH
 - stable between pH values of 5.0 and 9.0
D. Radiation
- Ultraviolet, x-ray, and high-energy particles
inactivate viruses.
E. Ether Susceptibility
- Ether susceptibility can be used to
distinguish viruses that possess an
envelope from those that do not.
F. Detergents
- Nonionic detergents (eg, Nonidet P40 and
Triton X-100) solubilize lipid constituents of
viral membranes.  highly organized fashion.
- Anionic detergents (eg, sodium dodecyl
sulfate) also solubilize viral envelopes; in
addition, they disrupt capsids into
separated polypeptides.
G. Formaldehyde
- destroys viral infectivity by reacting with
nucleic acid.
 Ether: sensitive  3. Uncoating: occurs concomitantly with or shortly
 Naked: Resistant
 Enveloped: Sensitive
H. Photodynamic Inactivation
- Viruses are penetrable to a varying degree
by vital dyes such as toluidine blue, neutral
red, and proflavine. These dyes bind to the
viral nucleic acid, and the virus then
becomes susceptible to inactivation by
visible light.
I. Antibiotics and Other Antibacterial Agents
- Antibacterial antibiotics and sulfonamides
have no effect on viruses.
- Larger concentrations of chlorine are
required to destroy viruses than to kill
bacteria
- Alcohols, such as isopropanol and ethanol,
are relatively ineffective against certain
viruses, especially picornaviruses.
J. Common Methods of Inactivating Viruses
for Various Purposes
- Sterilization may be accomplished by steam
under pressure, dry heat, ethylene oxide,
and γ-irradiation. Surface disinfectants
include sodium hypochlorite,
glutaraldehyde, formaldehyde, and
peracetic acid. Skin disinfectants include
chlorhexidine, 70% ethanol, and
iodophores. Vaccine production may involve
the use of formaldehyde, β-
propiolactone,psoralen + ultraviolet
irradiation, or detergents (subunit vaccines)
to inactivate the vaccine virus.
REPLICATION OF VIRUSES:
- Viruses multiply only in living cells. The
host cell must provide the energy and
synthetic machinery and the low-
molecular-weight precursors for the
synthesis of viral proteins and nucleic
acids. The viral nucleic acid carries the
genetic specificity to code for all of the
virus-specific macromolecules in a
GENERAL STEPS IN VIRAL REPLICATION
CYCLES
A. Attachment, Penetration, and Uncoating
1. Attachment: interaction of a virion with a
specific receptor site on the surface of a cell.
2. Penetration/engulfment: After binding, the virus
particle is taken up inside the cell.
after penetration. 
 is the physical separation of
the viral nucleic acid from the
outer structural components
of the virion so that it can
function.
The genome may be released as free nucleic acid
(picornaviruses) or as a nucleocapsid (reoviruses).
B. Replication and Assembly
- the replication mechanism depends on
the viral genome. 
- DNA viruses usually use host cell
proteins and enzymes to make
additional DNA that is transcribed to
messenger RNA (mRNA), which is then
used to direct protein synthesis.
- RNA viruses usually use the RNA core
as a template for synthesis of viral
genomic RNA and mRNA. 
- The viral mRNA directs the host cell to
synthesize viral enzymes and capsid
proteins, and to assemble new virions.
- Of course, there are exceptions to this
pattern. If a host cell does not provide
the enzymes necessary for viral
replication, viral genes supply the
information to direct synthesis of the
missing proteins. 
- Retroviruses, such as HIV, have an RNA
genome that must be reverse
transcribed into DNA, which then is
incorporated into the host cell genome.
To convert RNA into DNA, retroviruses must
contain genes that encode the virus-specific
enzyme reverse transcriptase, which transcribes an
RNA template to DNA. Reverse transcription never
occurs in uninfected host cells; the needed
enzyme, reverse transcriptase, is only derived from
the expression of viral genes within the infected
host cells. The fact that HIV produces some of its
own enzymes not found in the host has allowed
researchers to develop drugs that inhibit these
enzymes. These drugs, including the reverse
transcriptase inhibitor AZT, inhibit HIV replication
by reducing the activity of the enzyme without
affecting the host’s metabolism. This approach has
led to the development of a variety of drugs used to
treat HIV and has been effective at reducing the
number of infectious virions (copies of viral RNA) in
the blood to non-detectable levels in many HIV
infected individuals.
C. Release
- the last stage of viral replication
- release of the new virions produced in the
host organism. 
- They are then able to infect adjacent cells
and repeat the replication cycle.  vector (eg, arbo-viruses, now classified
- some viruses are released when the host
cell dies, while other viruses can leave
infected cells by budding through the
membrane without directly killing the cell.
1. Direct transmission from person to person
by contact. The major means of transmission
include droplet or aerosol infection (eg,
influenza, measles, smallpox); by sexual
contact (eg, papillomavirus, hepatitis B, herpes
simplex type 2, human immunodeficiency virus);
by hand–mouth, hand–eye, or mouth–mouth
contact (eg, herpes simplex, rhinovirus,
Epstein-Barr virus); or by exchange of
contaminated blood (eg, hepatitis B, human
immuno-deficiency virus).
2. Indirect transmission by the fecal–oral route
(eg, entero-viruses, rotaviruses, infectious
hepatitis A) or by fomites eg, Norwalk virus,
rhinovirus).
3. Transmission from animal to animal, with
humans an accidental host. Spread may be
by bite (rabies) or by droplet or aerosol infection
from rodent-contaminated quarters (eg,
arenaviruses, hantaviruses).
4. Transmission by means of an arthropod
primarily as togaviruses, flaviviruses, and
bunyaviruses).

PATHWAY TO VIRAL INFECTION: In influenza

virus infection, glycoproteins attach to a host
epithelial cell. As a result, the virus is engulfed.
RNA and proteins are made and assembled into
new virions.

NATURAL HISTORY (ECOLOGY) AND

MODES OF TRANSMISSION OF VIRUSES

 The mode of transmission used by a given

virus depends on the nature of the
interaction between the virus and the host.

Viruses may be transmitted in the following ways: