Basic Concept of Virology surface of the envelope.

These projections
are called peplomers.
GENERAL PROPERTIES OF VIRUSES

 Terms and definitions in Virology • Nucleocapsid

 Evolutionary origin of Viruses  The protein–nucleic acid complex
 Classifications of Viruses representing the packaged form of the viral
 Principles of Virus Structure genome. The term is commonly used in
 Chemical Composition of Viruses cases in which the nucleocapsid is a
 Cultivation and Assay of Viruses substructure of a more complex virus
 Laboratory Safety particle.
 Reaction To Physical And Chemical Agents
• Structural units
 Replication Of Viruses
 Natural History (Ecology) And  The basic protein building blocks of the
 Modes Of Transmission Of Viruses coat. They are usually a collection of more
than one non-identical protein subunit. The
TERMS AND DEFINITIONS IN VIROLOGY structural unit is often referred to as a
protomer.
• Viruses

 the smallest infectious agents (about 20 nm • Subunit

to 300 nm in diameter)  A single folded viral polypeptide chain.
 contain only one kind of nucleic acid (RNA
or DNA) as their genome. • Virion
 are inert in the extracellular environment;  The complete virus particle. In some
they replicate only in living instances (eg, papillomaviruses,
•Capsid picornaviruses), the virion is identical with
the nucleocapsid. In more complex virions
 The protein shell, or coat, that encloses the (herpesviruses, orthomyxoviruses), this
nucleic acid genome. includes the nucleocapsid plus a
surrounding envelope. This structure, the
• Capsomeres
virion, serves to transfer the viral nucleic
 Morphologic units seen in the electron acid from one cell to another.
microscope on the surface of icosahedral
EVOLUTIONARY ORIGIN OF VIRUSES
virus particles . Capsomeres represent
clusters of polypeptides, but the • The origin of viruses is not known, Two theories
morphologic units do not necessarily of viral origin can be summarized as follows:
correspond to the chemically defined
1. Viruses may be derived from DNA or RNA
structural units.
nucleic acid components of host cells that
• Defective virus became able to replicate autonomously and
evolve independently. They resemble genes
 A virus particle that is functionally deficient that have acquired the capacity to exist
in some aspect of replication. independently of the cell. Some viral
sequences are related to portions of cellular
• Envelope
genes encoding protein functional domains.
 A lipid-containing membrane that surrounds It seems likely that at least some viruses
some virus particles. It is acquired during evolved in this fashion.
viral maturation by a budding process 2. Viruses may be degenerate forms of
through a cellular membrane. Virus- intracellular parasites. There is no evidence
encoded glycoproteins are exposed on the that viruses evolved from bacteria, although
 other obligately intracellular organisms (eg, relationships, pathogenicity, tissue tropisms,
rickettsiae and chlamydiae) presumably did and pathology.
so. However, poxviruses are so large and
complex that they might represent B. Universal System of Virus Taxonomy
evolutionary products of some cellular  A system has been established in which
ancestor. viruses are separated into major groupings
—called families—on the basis of virion
CLASSIFICATION OF VIRUSES
morphology, genome structure, and
A. Basis of Classification strategies of replication. Virus family names
have the suffix -viridae.
The following properties have been used as a
basis for the classification of viruses.  Within each family, subdivisions called
genera are usually based on biological,
1. Virion morphology: including size, shape, genomic, physicochemical, or serologic
type of symmetry, presence or absence of differences. Criteria used to define genera
peplomers, and presence or absence of vary from family to family. Genus names
membranes. carry the suffix -virus. In several families
2. Virus genome properties: including type of (Herpesviridae, Paramyxoviridae,
nucleic acid (DNA or RNA), size of genome Parvoviridae, Poxviridae, Reoviridae,
in kilobases (kb) or kilobase pairs (kbp), Retroviridae), a larger grouping called
strandedness (single or double), whether subfamilies has been defined, reflecting the
linear or circular, sense (positive, negative, complexity of relationships among member
ambisense),segments (number, size), viruses. Virus orders may be used to group
nucleotide sequence, G + C content, and virus families that share common
presence of special features characteristics. For example, order
(repetitiveelements, isomerization, 5′- Mononegavirales encompasses the
terminal cap, 5′-terminal covalently linked Bornaviridae, Filoviridae, Paramyxoviridae,
protein, 3′- terminal poly(A) tract). and Rhabdoviridae families.
3. Genome organization and replication:  By 2000, the International Committee on
including gene order, number and position Taxonomy of Viruses had organized more
of open reading frames,strategy of than 4000 animal and plant viruses into 56
replication (patterns of transcription, families and 233 genera, with hundreds of
translation), and cellular sites (accumulation viruses still unassigned.
of proteins, virion assembly, virion release).  Of these, 24 families contained viruses that
4. Virus protein properties: including infect humans and animals.
number, size, and functional activities of
structural and nonstructural proteins, amino C. Survey of DNA-Containing Viruses
acid sequence, modifications (glycosylation,
A. Parvoviruses
phosphorylation, myristylation), and special
B. Anelloviruses
functional activities (transcriptase, reverse
C. Polyomaviruses
transcriptase, neuraminidase, fusion
D. Papillomaviruses
activities).
E. Adenoviruses
5. Antigenic properties.
F. Hepadnaviruses
6. Physicochemical properties of the virion:
G. Herpesviruses
including molecular mass, buoyant density,
H. Poxviruses
pH stability, thermal stability, and
susceptibility to physical and chemical A. PARVOVIRUSES
agents, especially ether and detergents.
7. Biologic properties: including natural host  are very small viruses with a particle size of
range, mode of transmission, vector about 18–26 nm.
  cubic symmetry, with 32 capsomeres, no  Most animal species harbor one or more
envelope. polyomaviruses. They produce chronic
 The genome is linear, single-stranded DNA, infections in their natural hosts, and most
5.6 kb in size. mammalian viruses can induce tumors in
 Replication occurs only in actively dividing some animal species.
cells; capsid assembly takes place in the
D. PAPILLOMAVIRUSES
nucleus of the infected cell.
 Many parvoviruses replicate autonomously,  similar to polyomaviruses in some respects
but the adenoassociated satellite viruses but with a larger genome (8 kbp) and
are defective, requiring the presence of an particle size (55 nm).
adenovirus or herpesvirus as “helper.”  There are many genotypes of human
 Human parvovirus B19 replicates in papillomaviruses, also k nown as “wart”
immature erythroid cells and causes several viruses; certain types are causative agents
adverse consequences, including aplastic of genital cancers in humans.
crisis, fifth disease, and fetal death.  are very host and tissue specific and cannot
be grown in cultured cells in vitro.
B. ANELLOVIRUSES
 Many animal species carry
 are small (~30 nm in diameter) papillomaviruses.
 icosahedral virions that lack an envelope.
E. ADENOVIRUSES
 The viral genome is circular, single-stranded
DNA, 2.0–3.9 kb in size.  Adenoviruses are medium-sized (70–90
 The genome is negative sense. -include the nm)
torque teno viruses.  nonenveloped viruses exhibiting cubic
 globally distributed in the human population symmetry, with 252 capsomeres.
and are also found in many animal species.  Fibers protrude from the vertex
No specific disease associations have been capsomeres.
proven. There is limited knowledge about  The genome is linear, double-stranded
viral gene expression and replication. DNA, 26–45 kbp in size.
 Replication occurs in the nucleus.
C. POLYOMAVIRUSES
 Complex splicing patterns produce mRNAs.
 are small (45 nm)  At least 51 types infect humans, especially
 nonenveloped, heat-stable, ether-resistant in mucous membranes, and some types can
viruses exhibiting cubic symmetry, with 72 persist in lymphoid tissue.
capsomeres.  Some adenoviruses cause acute respiratory
 The genome is circular, double-stranded diseases, conjunctivitis, and gastroenteritis.
DNA,5 kbp in size. Some human adenoviruses can induce
 These agents have a slow growth cycle, tumors in newborn hamsters. Many
stimulate cell DNA synthesis, and replicate serotypes infect animals.
within the nucleus.
F. HEPADNAVIRUSES
 The most well-known human
polyomaviruses are JC virus, the causative  Hepadnaviruses are small (40–48 nm)
agent of progressive multifocal viruses -containing circular double-
leukoencephalopathy; BK virus, associated stranded DNA molecules that are 3.2
with nephropathy in transplant recipients; kbp in size.
and Merkel cell virus, found associated with  The viral DNA in the particles contains a
the majority of Merkel cell skin carcinomas. large single-stranded gap.
SV40, a primate virus, can also infect  Replication involves repair of the single-
humans. 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 - ether-resistant, nonenveloped viruses
high density; other enteroviruses are having icosahedral symmetry.
acid stable and have a lower density. - Particles have two or three protein shells
- Picornaviruses infecting animals include with channels extending from the
foot-and-mouth disease of cattle and surface to the core; short spikes extend
encephalomyocarditis of rodents. from the virion surface.
- The genome is linear, double-stranded,
B. ASTROVIRUSES segmented RNA (10–12 segments),
- similar in size to picornaviruses (28–30 totaling 16–27 kbp in size.
nm), - Individual RNA segments range in size
- particles display a distinctive star- from 680 bp to 3900 bp.
shaped outline on their surfaces - Replication occurs in the cytoplasm;
- The genome is linear, positive-sense, genome segment reassortment occurs
single-stranded RNA, 6.4–7.4 kb in size. readily.
- These agents may be associated with - Reoviruses of humans include
gastroenteritis in humans and animals rotaviruses, which have a distinctive
wheel-shaped appearance and
C. CALICIVIRUSES cause gastroenteritis.
- are similar to picornaviruses but slightly - Antigenically similar reoviruses infect
larger (27–40 nm) many animals.
- The particles appear to have cup- - The genus Coltivirus includes Colorado
shaped depressions on their surfaces tick fever virus of humans.
- The genome is single-stranded, positive-
sense RNA, 7.4–8.3 kb in size; the virion G. ARBOVIRUSES AND RODENT-BORNE
has no envelope VIRUSES
- Important human pathogens are the - are ecologic groupings (not a virus
noroviruses (eg, Norwalk virus), the family) of viruses with diverse physical
cause of epidemic acute gastroenteritis. and chemical properties.
- Other agents infect cats and sea lions - The arboviruses (there are more than
as well as primates 350 of them) have a complex cycle
involving arthropods as vectors that
D. HERPESVIRUSES transmit the viruses to vertebrate hosts
- similar to caliciviruses. The particles are by their bite.
small (27–34 nm) and ether resistant. - Viral replication does not seem to harm
- The genome is single-stranded, positive- the infected arthropod
sense RNA, 7.2 kb in size. - Arboviruses infect humans, mammals,
- It lacks a genome-linked protein (VPg). birds, and snakes and use mosquitoes
- Human hepatitis E virus belongs to this and ticks as vectors.
group. - Human pathogens include dengue,
yellow fever, West Nile fever, and
E. PICOBIRNAVIRUSES encephalitis viruses.
- are small (35–40 nm) - Rodent-borne viruses establish
- non-enveloped viruses with icosahedral persistent infections in rodents and are
structure. transmitted without an arthropod vector.
- The genome is linear, double-stranded, - Human diseases include hantavirus
segmented (bipartite) RNA (2 infections and Lassa fever
segments), total in 4.0–4.5 kb - The viruses in these ecologic groupings
belong to several virus families,
F. REOVIRUSES including arenavirus, bunyavirus,
- are medium-sized (60–80 nm), flavivirus, reovirus, rhabdovirus, and
togavirus
 - Lassa fever virus of Africa is one
H. TOGAVIRUSES example. These viruses require
- Many arboviruses that are major human maximum containment conditions in the
pathogens, called alphaviruses—as well laboratory.
as rubella virus—belong to this group.
- They have a lipid-containing envelope K. CORONAVIRUSES
and are ether sensitive, and their - Coronaviruses are enveloped 120- to
genome is single-stranded, positive- 160-nm particles containing an
sense RNA, 9.7–11.8 kb in size. unsegmented genome of positive-sense,
- The enveloped virion measures 70 nm. single-stranded RNA, 27–32 kb in size;
The virus particles mature by budding the nucleocapsid is helical,9–11 nm in
from host cell membranes. diameter.
- An example is eastern equine - Coronaviruses resemble
encephalitis virus. Rubella orthomyxoviruses but have petal-shaped
virus has no arthropod vector surface projections arranged in a fringe,
similar to a solar corona.
I. FLAVIVIRUSES - Coronavirus nucleocapsids develop in
- are enveloped viruses, 40–60 nm in the cytoplasm and mature by budding
diameter, containing single- stranded, into cytoplasmic vesicles. These viruses
positive-sense RNA. have narrow host ranges.
- Genome sizes vary from 9.5 kb - Most human coronaviruses cause mild
(hepatitis C) to 11 kb (flaviviruses) to acute upper respiratory tract illnesses
12.5 kb (pestiviruses) —“colds”—but a new coronavirus
- Mature virions accumulate within identified in 2003 causes a severe
cisternae of the endoplasmic reticulum. acute respiratory syndrome (SARS).
This group of arboviruses includes - Toroviruses, which cause
yellow fever virus and dengue viruses. gastroenteritis, form a distinct genus.
Most members are transmitted by blood- Coronaviruses of animals readily
sucking arthropods. Hepatitis C virus establish persistent infections and
has no known vector include mouse hepatitis virus and avian
infectious bronchitis virus.

J. ARENAVIRUSES L. RETROVIRUSES
- are pleomorphic, enveloped viruses - are spherical, enveloped viruses (80–
ranging in size from 50 nm to 300 nm 110 nm in diameter)
(mean, 110–130 nm). - genome contains two copies of linear,
- The genome is segmented, circular, positive-sense, single-stranded RNA of
single-stranded RNA the same polarity as viral mRNA.
- is negative sense and ambisense, 10– - Each monomer RNA is 7–11 kb in size.
14 kb in total size Particles contain a helical nucleocapsid
- Replication occurs in the cytoplasm with within an icosahedral capsid. Replication
assembly via budding on the plasma is unique; the virion contains a
membrane. reverse transcrip-tase enzyme that
- The virions incorporate host cell produces a DNA copy of the RNA
ribosomes during maturation, which genome.
gives the particles a “sandy” appearance - This DNA becomes circularized and
- Most members of this family are unique integrated into host chromosomal DNA.
to tropical America (ie, the Tacaribe The virus is then replicated from the
complex). integrated “provirus” DNA copy.
- All arenaviruses pathogenic for humans - Virion assembly occurs by budding on
cause chronic infections in rodents plasma membranes.
- Hosts remain chronically infected.
 - are widely distributed; there are also - The genome is made up of a triple-
endogenous proviruses resulting from segmented, circular, single-stranded,
ancient infections of germ cells negative-sense or ambisense RNA, 11–
transmitted as inherited genes in most 19 kb in overall size.
species. - Virion particles contain three circular,
- Leukemia and sarcoma viruses of helically symmetric nucleocapsids about
animals and humans, foamy viruses of 2.5 nm in diameter and 200–3000 nm in
primates, and lentiviruses (human length.
immuno-deficiency viruses; visna of - Replication occurs in the cytoplasm, and
sheep) are included in this group. an envelope is acquired by budding into
Retroviruses cause acquired immuno- the Golgi. The majority of these viruses
deficiency syndrome (AIDS) and make are transmitted to vertebrates by
possible the identification of cellular arthropods (arboviruses).
oncogenes - Hantaviruses are transmitted not by
arthropods but by persistently infected
M. ORTHOMYXOVIRUSES rodents via aerosols of contaminated
- are medium-sized, 80- to 120-nm excreta.
enveloped viruses exhibiting helical - They cause hemorrhagic fevers and
symmetry. nephropathy as well as a severe
- Particles are either round or filamentous, pulmonary syndrome.
with surface projections that contain
hemagglutinin or neuraminidase activity. O. BORNAVIRUSES
- The genome is linear, segmented, - are enveloped, spherical (80–125 nm)
negative-sense, single-stranded RNA, viruses.
totaling 10–13.6 kb in size. - The genome is linear, single-stranded,
- Segments range from 900 to 2350 nonsegmented, negative-sense RNA,
nucleotides each. 8.5–10.5 kb in size.
- The internal nucleoprotein helix - Unique among nonsegmented,
measures 9–15 nm. negative-sense RNA viruses, replication
- During replication, the nucleocapsid is and transcription of the viral genome
assembled in the nucleus; the occur in the nucleus.
hemagglutinin and neuraminidase - Borna disease virus is neurotropic in
accumulate in the cytoplasm. The virus animals; a postulated association with
matures by budding at the cell neuropsychiatric disorders of humans is
membrane. unproved
- All orthomyxoviruses are influenza
viruses that infect humans or animals. P. RHABDOVIRUSES
- The segmented nature of the viral - are enveloped virions resembling a
genome permits ready genetic bullet, flat at one end and round at the
reassortment when two influenza other, measuring about 75 × 180 nm.
viruses infect the same cell, presumably - The envelope has 10-nm spikes.
fostering the high rate of natural - The genome is linear, single-stranded,
variation among influenza viruses. nonsegmented, negative-sense RNA,
- Transmission from other species is 13–16kb in size.
thought to explain the emergence of - Particles are formed by budding from
new human pandemic strains of the cell membrane.
influenza Aviruses. - Viruses have broad host ranges.
- Rabies virus is a member of this group.
N. BUNYAVIRUSES
- are spherical or pleomorphic, 80- to 120- Q. PARAMYXOVIRUSES
nm enveloped particles.
 - are similar to but larger (150–300 nm) - Viroids replicate by an entirely novel
than orthomyxoviruses mechanism.
- Particles are pleomorphic. - Viroid RNA does not encode any protein
- The internal nucleocapsid measures 13– products; the devastating plant diseases
18 nm, and the linear, induced by viroids occur by an unknown
single-stranded, nonsegmented, mechanism.
negative-sense RNA is 16–20 kb - To date, viroids have been detected only
in size. in plants; none have been demonstrated
- Both the nucleocapsid and the to exist in animals or humans.
hemagglutinin are formed in the
cytoplasm. U. PRIONS
- Those infecting humans include mumps, - are infectious particles composed solely
measles, parainfluenza, metapneumo, of protein with no detectable nucleic acid
and respiratory syncytial viruses. - They are highly resistant to inactivation
- These viruses have narrow host ranges. by heat, formaldehyde, and ultraviolet
In contrast to influenza viruses, light that inactivate viruses
paramyxoviruses are genetically stable. - The prion protein is encoded by a single
cellular gene. Prion diseases, called
R. FILOVIRUSES “transmissible spongiform
- are enveloped, pleomorphic viruses that encephalopathies,” include scrapie in
may appear very long and threadlike. sheep, mad cow disease in cattle,
- They typically are 80 nm wide and about and kuru and Creutzfeldt-Jakob disease
1000 nm long. in humans. Prions do not appear to be
- The envelope contains large peplomers. viruses.
- The genome is linear, negative-sense,
single-stranded RNA, 19 kb in size.
Marburg and Ebola viruses cause PRINCIPLES OF VIRUS STRUCTURE
severe hemorrhagic fever in Africa.  shapes and sizes.
- These viruses require maximum  Structural information is necessary for virus
containment conditions (Biosafety Level classification and for establishing structure–
4) for handling function relationships of viral proteins.
 The particular structural features of each
S. OTHER VIRUSES virus family are determined by the functions
- There is insufficient information to permit of the virion: morphogenesis and release
classification of from infected cells; transmission to new
some viruses. This applies to some hosts; and attachment, penetration, and
viruses of gastroenteritis. uncoating in newly infected cells
 Knowledge of virus structure furthers our
understanding of the mechanisms of certain
T. VIROIDS processes such as the interaction of virus
- are small infectious agents that cause particles with cell surface receptors and
neutralizing antibodies. It may lead also to
diseases of plants.
the rational design of antiviral drugs capable
- are agents that do not fit the definition of
of blocking viral attachment, uncoating, or
classic viruses.
assembly in susceptible cells.
- They are nucleic acid molecules without
a protein coat.
- Plant viroids are single-stranded, TYPES OF SYMMETRY OF VIRUS PARTICLES
covalently closed circular RNA  Electron microscopy, cryoelectron
molecules consisting of about 360 microscopy, and x-ray diffraction techniques
nucleotides and with a highly base-
paired rodlike structure. I. STANDARD ELECTRON MICROSCOPY:
 - The study of viral symmetry - Genetic economy requires that a viral
- requires heavy metal stains (eg, structure be made from many identical
potassium phosphotungstate) to molecules of one or a few proteins
emphasize surface structure - Viral architecture can be grouped into
- resolve fine differences in the basic three types based on the arrangement
morphology of viruses of morphologic subunits:
- The heavy metal permeates the virus 1. cubic symmetry (eg,
particle like a cloud and brings out the adenoviruses)
surface structure of viruses by virtue of 2. helical symmetry (eg,
“negative staining” orthomyxoviruses)
- The typical level of resolution is 3–4 nm. 3. complex structures (eg,
- However, conventional methods of poxviruses).
sample preparation often cause
distortions and changes in particle 2. HELICAL SYMMETRY
morphology - protein subunits are bound in a periodic
way to the viral nucleic acid, winding it
II. CRYOELECTRON MICROSCOPY into a helix.
- uses virus samples quick frozen in - The filamentous viral nucleic acid–
vitreous ice protein complex (nucleocapsid) is then
- fine structural features are preserved, coiled inside a lipid-containing envelope.
the use of negative stains is avoided. - Thus, as is not the case with icosahedral
- Three-dimensional structural information structures, there is a regular, periodic
can be obtained by the use of computer interaction between capsid protein and
image processing procedures. nucleic acid in viruses with helical
symmetry. It is not possible for “empty”
III. X-RAY CRYSTALLOGRAPHY helical particles to form.
- can provide atomic resolution - All known examples of animal viruses
information, generally at a level of with helical symmetry contain RNA
0.2–0.3 nm. genomes and, with the exception of
- specimen must be crystalline, and this rhabdoviruses, have flexible
has only been achieved with small, nucleocapsids that are wound into a ball
nonenveloped viruses. inside envelopes
- However, it is possible to obtain high-
resolution structural data on well-defined 3. COMPLEX STRUCTURES
substructures prepared from the more - Some virus particles do not exhibit
complex viruses. simple cubic or helical symmetry but are
more complicated in structure. For
1. CUBIC SYMMETRY example, poxviruses are brick shaped,
- icosahedral pattern with ridges on the external surface and a
- 20 faces (each an equilateral triangle), core and lateral bodies inside.
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.
  - 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
 MEASURING THE SIZES OF VIRUS proteins or glycoproteins exposed on the
- Small size and the ability to pass through surface of the virus particle. Some surface
filters that hold back bacteria are classic proteins may also exhibit specific activities
attributes of viruses.  (eg, influenza virus hemagglutinin
- However, because some bacteria may be agglutinates red blood cells).
smaller than the largest viruses, filter ability - The enzymes are present in very small
is not regarded as a unique feature of amounts and are probably not important in
viruses. the structure of the virus particles; however,
- electron microscope they are essential for the initiation of the
- sedimentation in the ultracentrifuge. viral replicative cycle when the virion enters
- Direct observation in the electron a host cell.
microscope is the most widely used method
for estimating particle size.  VIRAL NUCLEIC ACID
- Another method that can be used is -either DNA or RNA 
sedimentation in the ultracentrifuge. The -The genome may be single or double
relationship between the size and shape of stranded, circular or linear, and segmented
a particle and its rate of sedimentation or non-segmented. 
permits determination of particle size. - The type of nucleic acid, its strandedness,
and its size are major characteristics used
COMPARATIVE MEASUREMENTS for classifying viruses into families
 VIRAL LIPID ENVELOPES
- Viruses range in diameter from about 20 nm - A number of different viruses contain lipid
to 300 nm envelopes as part of their structure.
- Particles with a twofold difference in - Derived from the host cell
diameter have an eightfold difference in
- The lipid is acquired when the viral
volume.
nucleocapsid buds through a cellular
- Thus, the mass of a poxvirus is about 1000
membrane in the course of maturation.
times greater than that of the poliovirus
Budding occurs only at sites where virus-
particle, and the mass of a small bacterium
specific proteins have been inserted into the
is 50,000 times greater.
host cell membrane. The budding process
- Staphylococcus species have a diameter of
varies markedly depending on the replication
about 1000 nm (1 μm).
strategy of the virus and the structure of the
- particle size: Pox: 230x400 nm
nucleocapsid. 
- polio: 45nm
- Lipid-containing viruses are sensitive to
treatment with ether and other organic
CHEMICAL COMPOSITION OF VIRUSES
solvents, indicating that disruption or loss of
lipid results in loss of infectivity.
 VIRAL PROTEIN
- Nonlipid-containing viruses are generally
- major purpose is to facilitate transfer of the
resistant to ether.
viral nucleic acid from one host cell to
another.
Viruses contain a single kind of nucleic acid—either Many viruses are human pathogens, and
DNA or RNA—that encodes the genetic information laboratory-acquired infections can occur.
necessary for replication of the virus. Laboratory procedures are often potentially
hazardous if proper technique is not followed.
 VIRAL GLYCOPROTEINS Among the common hazards that might expose
- Viral envelopes contain glycoproteins laboratory personnel to the risk of infection are the
- the envelope glycoproteins are virus following:
encoded
- The surface glycoproteins of an enveloped  RISK OF INFECTION
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 infected tissues, centrifugation, ultrasonic
membrane fusion step of infection.  vibration, or broken glassware; 
- The glycoproteins are also important viral 2. ingestion—from mouth pipetting, eating or
antigens. As a result of their position at the smoking in the laboratory, or inadequate
outer surface of the virion, they are washing of hands; 
frequently involved in the interaction of the 3. skin penetration—from needle sticks, broken
virus particle with neutralizing antibody. glassware, hand contamination by leaking
containers, handling of infected tissues, or
CULTIVATION AND ASSAY OF VIRUSES animal bites; and
4. splashes into the eye.
 Cultivation of Viruses
- cell cultures or in fertile eggs  GOOD BIOSAFETY PRACTICES
- Growth of virus in animals is still used for the 1. training in and use of aseptic techniques
primary isolation of certain viruses and for
2. interdiction of mouth pipetting
studies of the pathogenesis of viral diseases
3. no eating, drinking, or smoking in the laboratory
and of viral oncogenesis.
4. use of personal protective equipment (eg,
Many viruses can be grown in cell cultures or in
fertile eggs under strictly controlled conditions. coats, gloves, masks) not to be worn outside
the laboratory
3 BASIC TYPES OF CELL CULTURES: 5. sterilization of experimental wastes
6. use of biosafety hoods
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 facilities (Biosafety Level 4) are necessary when
passages in culture. personnel are working with high-risk agents such
as the filoviruses and rabies virus.
2. Diploid cell lines: 
REACTION TO PHYSICAL AND CHEMICAL
- secondary cultures 
AGENTS
- have undergone a change that allows their
A. Heat and Cold :
limited culture (up to 50 passages) but that
- Icosahedral viruses: losing little infectivity at
retain their normal chromosome pattern.
37°C for several hours 
3. Continuous cell lines - Generally destroyed by heating at 50-60° C
for 30 mins
 cultures capable of more prolonged - - Preserved : subfreezing temperatures ;
perhaps indefinite-growth that have been lyophilization and preserved at dry state at
derived from diploid cell lines or from 4°C 
malignant tissues. B. Stabilization of Viruses by Salts
- MgCl2, 1 mol/L, stabilizes picornaviruses
The type of cell culture used for viral cultivation and reoviruses; 
depends on the sensitivity of the cells to a particular - MgSO4, 1 mol/L, stabilizes
virus. orthomyxoviruses and paramyxoviruses
- Na2SO4, 1 mol/L, stabilizes herpesviruses.
LABORATORY SAFETY C. pH
 - stable between pH values of 5.0 and 9.0
D. Radiation REPLICATION OF VIRUSES:
- Ultraviolet, x-ray, and high-energy particles
inactivate viruses. - Viruses multiply only in living cells. The
E. Ether Susceptibility host cell must provide the energy and
- Ether susceptibility can be used to synthetic machinery and the low-
distinguish viruses that possess an molecular-weight precursors for the
envelope from those that do not. synthesis of viral proteins and nucleic
F. Detergents acids. The viral nucleic acid carries the
- Nonionic detergents (eg, Nonidet P40 and genetic specificity to code for all of the
Triton X-100) solubilize lipid constituents of virus-specific macromolecules in a
viral membranes.  highly organized fashion.
- Anionic detergents (eg, sodium dodecyl
GENERAL STEPS IN VIRAL REPLICATION
sulfate) also solubilize viral envelopes; in
CYCLES
addition, they disrupt capsids into
separated polypeptides.
A. Attachment, Penetration, and Uncoating
G. Formaldehyde
1. Attachment: interaction of a virion with a
- destroys viral infectivity by reacting with
specific receptor site on the surface of a cell.
nucleic acid.
2. Penetration/engulfment: After binding, the virus
particle is taken up inside the cell.
 Ether: sensitive  3. Uncoating: occurs concomitantly with or shortly
 Naked: Resistant after penetration. 
 Enveloped: Sensitive  is the physical separation of
the viral nucleic acid from the
H. Photodynamic Inactivation outer structural components
- Viruses are penetrable to a varying degree of the virion so that it can
by vital dyes such as toluidine blue, neutral function.
red, and proflavine. These dyes bind to the The genome may be released as free nucleic acid
viral nucleic acid, and the virus then (picornaviruses) or as a nucleocapsid (reoviruses).
becomes susceptible to inactivation by
visible light. B. Replication and Assembly
I. Antibiotics and Other Antibacterial Agents - the replication mechanism depends on
- Antibacterial antibiotics and sulfonamides the viral genome. 
have no effect on viruses. - DNA viruses usually use host cell
- Larger concentrations of chlorine are proteins and enzymes to make
required to destroy viruses than to kill additional DNA that is transcribed to
bacteria messenger RNA (mRNA), which is then
- Alcohols, such as isopropanol and ethanol, used to direct protein synthesis.
are relatively ineffective against certain - RNA viruses usually use the RNA core
viruses, especially picornaviruses. as a template for synthesis of viral
J. Common Methods of Inactivating Viruses genomic RNA and mRNA. 
for Various Purposes - The viral mRNA directs the host cell to
- Sterilization may be accomplished by steam synthesize viral enzymes and capsid
under pressure, dry heat, ethylene oxide, proteins, and to assemble new virions.
and γ-irradiation. Surface disinfectants - Of course, there are exceptions to this
include sodium hypochlorite, pattern. If a host cell does not provide
glutaraldehyde, formaldehyde, and the enzymes necessary for viral
peracetic acid. Skin disinfectants include replication, viral genes supply the
chlorhexidine, 70% ethanol, and information to direct synthesis of the
iodophores. Vaccine production may involve missing proteins. 
the use of formaldehyde, β- - Retroviruses, such as HIV, have an RNA
propiolactone,psoralen + ultraviolet genome that must be reverse
irradiation, or detergents (subunit vaccines) transcribed into DNA, which then is
to inactivate the vaccine virus. incorporated into the host cell genome.
To convert RNA into DNA, retroviruses must
contain genes that encode the virus-specific 1. Direct transmission from person to person
enzyme reverse transcriptase, which transcribes an by contact. The major means of transmission
RNA template to DNA. Reverse transcription never include droplet or aerosol infection (eg,
occurs in uninfected host cells; the needed influenza, measles, smallpox); by sexual
enzyme, reverse transcriptase, is only derived from contact (eg, papillomavirus, hepatitis B, herpes
the expression of viral genes within the infected simplex type 2, human immunodeficiency virus);
host cells. The fact that HIV produces some of its by hand–mouth, hand–eye, or mouth–mouth
own enzymes not found in the host has allowed contact (eg, herpes simplex, rhinovirus,
researchers to develop drugs that inhibit these Epstein-Barr virus); or by exchange of
enzymes. These drugs, including the reverse contaminated blood (eg, hepatitis B, human
transcriptase inhibitor AZT, inhibit HIV replication immuno-deficiency virus).
by reducing the activity of the enzyme without
affecting the host’s metabolism. This approach has 2. Indirect transmission by the fecal–oral route
led to the development of a variety of drugs used to (eg, entero-viruses, rotaviruses, infectious
treat HIV and has been effective at reducing the hepatitis A) or by fomites eg, Norwalk virus,
number of infectious virions (copies of viral RNA) in rhinovirus).
the blood to non-detectable levels in many HIV
infected individuals. 3. Transmission from animal to animal, with
humans an accidental host. Spread may be
C. Release by bite (rabies) or by droplet or aerosol infection
- the last stage of viral replication from rodent-contaminated quarters (eg,
- release of the new virions produced in the arenaviruses, hantaviruses).
host organism. 
- They are then able to infect adjacent cells 4. Transmission by means of an arthropod
and repeat the replication cycle.  vector (eg, arbo-viruses, now classified
- some viruses are released when the host primarily as togaviruses, flaviviruses, and
cell dies, while other viruses can leave bunyaviruses).
infected cells by budding through the
membrane without directly killing the cell.

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: