INTRODUCTION TO MEDICAL VIROLOGY
(Structure, Classification & Replication)
Understand the basic concept viral structure
And related medical importance .
Viral classification and toxonomy
Describe the steps of viral replication cycle and
its important .
ﻣﻨﻴﺮ اﻟﺠﻐﺪاف.د
Differences Between Different Groups of Microorganisms
Growth on
Whether they Whether they
artifici Division by Whether they Their sensitivity
have both have
al binary have to
DNA and muramic
media fission ribosomes antibiotics
RNA acid
Bacteria Yes Yes Yes Yes Yes Yes
Mycoplasm
Yes Yes Yes Yes No Yes
a
Rickettsia No Yes Yes Yes Yes Yes
Chlamydia No Yes Yes Yes No Yes
Viruses No No No No * No No
* The arenavirus family (an RNA virus family) appears to package ribosomes
'accidentally'. The packaged ribosomes appear to play no role in viral protein
synthesis
Viruses: General Properties
1. Small size:
o The smallest infectious agents
(20-300 nm in diameter)
o Bacteria (300-1000nm); RBC (7500nm)
2. Genome:
o Either DNA or RNA
3. Metabolically inert:
o Do not posses active protein synthesizing
apparatus
o Do not have a nucleus, cytoplasm,
mitochondria or ribosomes
o No metabolic activity outside host: obligate
intracellular parasites
o Can replicate only inside living cells; NOT on
inanimate media
Lipid Envelope Nucleic Acid
Protein
Capsid
Virion
Associated
Spike
Polymerase
Projections
Viruses: Structure
• Genome:
o A core of DNA or RNA
o May be single-stranded (ss) or double stranded (ds)
o May be circular or linear
• Capsid: protein coat surrounding the genome
o Provides structural symmetry
o Participates in attachment to susceptible host
o Facilitates transfer of viral nucleic acid in to host cell
o Protects the viral genome from nucleases in blood stream
• Capsomeres: the structural units making up capsid:
consist of one or several proteins
Viruses: Structure
Other Viral Proteins
Outer viral proteins are antigenic and induce
neutralizing antibodies and activate Tc cells to kill
virus-infected cells. This ccurs in natural infections
and immunization
Some virus proteins act as superantigns like EBV and
CMV
Some viruses like HSV and CMV contain regulatory
proteins located in tegument present between
nucleocapsid and envelope
Viruses: Structure
Envelope:
o A lipoprotein surrounding the capsid in some
viruses
o May contain material of host cell as well as viral
origin.
o Virus-encoded glycoproteins are exposed on the
surface of the envelope
o Most human helical viruses are enveloped while
icosahedral are either enveloped or non-
enveloped
Nucleocapsid
o The protein-nucleic acid complex
Virion
o The complete infective virus particle
Viruses: Structure
Significance of Envelope
o Enveloped viruses are more unstable i.e. are
more sensitive to heat, drying, detergents
and alcohols
o All viruses transmitted by feco-oral route like
HAV, poliovirus rotavirus are non-enveloped
(those have to survive in environment)
o Enveloped viruses are often transmitted by
direct contact as by blood, sexual contact
like HIV, HBV, HCV, rabies virus, measels,
mumps, rubella viruses etc
Viruses: Symmetry (Shapes)
1. Cubic Symmetry
(Icosahedral)
• Have exactly 60 subunits
on the surface of an
icosahedron
• Have fivefold, threefold
and twofold rotational
symmetry
Viruses: Symmetry (Shapes)
2. Helical Symmetry Nucleic acid
• The virion contains an
elongated nucleocapsid Protein subunits
• The capsomeres are
arranged round the spiral of
nucleic acid
• Most helical viruses are
enveloped
Viruses: Symmetry (Shapes)
• 3. Complex symmetry
• Does not conform to
cubic or helical
symmetry
Viruses: Classification
Basis of Classification
1. Morphology
2. Genome Properties
o Type of nucleic acid (DNA or RNA)
o Single or double stranded
o Genome organization & replication
3. Protein Properties
4. Antigenic Properties
5. Biologic Properties
o Natural host range
o Mode of transmission
o Vectors
o Pathogenicity
CLASSIFICATION
NUCLEIC ACID
• RNA or DNA
• segmented or non-segmented
• linear or circular
• single-stranded or double-stranded
• if single-stranded RNA
– is genome mRNA (+) sense or
complementary to mRNA (-) sense
Dr.T.V.Rao MD 15
Viruses: Nomenclature
Family
(have the suffix –viridae)
e.g. Poxviridae
Subfamilies
(in Poxvirinae, Herpesvirinae
Parvovirinae & paramyxovirinae)
Genera
(have the suffix –virus) Viruses in 24 families
e.g. Parvoviruses infect humans & animals
DNA viruses
From Principles of
Virology Flint et al
ASM Press
Dr.T.V.Rao MD 18
Dr.T.V.Rao MD 19
RNA VIRUSES
SINGLE STRANDED SINGLE STRANDED DOUBLE STRANDED
positive sense negative sense
ENVELOPED NONENVELOPED ENVELOPED NONENVELOPED
ICOSAHEDRAL HELICAL ICOSAHEDRAL HELICAL ICOSAHEDRAL
FLAVIVIRIDAE CORONAVIRIDAE PICORNAVIRIDAE ORTHOMYXOVIRIDAE REOVIRIDAE
TOGAVIRIDAE CALICIVIRIDAE PARAMYXOVIRIDAE
RETROVIRIDAE ASTROVIRIDAE RHABDOVIRIDAE
FILOVIRIDAE
BUNYAVIRIDAE
ARENAVIRIDAE
Dr.T.V.Rao MDfrom Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991
Modified 22
Viral Replication
Viral Growth Curve
When one virion infects a cell, it can replicate in hours to produce
hundreds of virions within that cell: viruses spread rapidly from cell
to cell
The time required for the growth cycle varies from minutes for
some bacterial viruses and hours for some human viruses...."
Eclipse period
Viral Replication
Viral Growth Curve
Eclipse Period
The time during which no virus is found inside the cell
Latent Period
Time from onset of infection to the appearance of
extracellularly
Cytopathic Effect (CPE)
Alteration of cell morphology accompanied by marked
derangement of cell function toward the end of latent
period
Virus Replication
1 Virus attachment
and entry
1 2 Uncoating of virion
3 Migration of
genome nucleic
5 acid to nucleus
4 Transcription
4
2 5 Genome replication
3 6 Translation of virus
mRNAs
7 Virion assembly
7
8 Release of new
virus particles
6
8
Dr.T.V.Rao MD 25
Virus Replication
Virus Replication
1) ATTACHMENT (Adsorption)
• Binding of a Viral Attachment
Protein (VAP) to a Receptor on cell
• Receptor molecules are usually
glycoproteins
• Presence of specific receptors on
the surface of cells determines the
TROPISM of most viruses
• Best occurs at 37oC
Attachment of virus to receptor on
host cell membrane. B. Antibody
prevents adsorption of virus.
RECEPTOR VIRUS
ICAM-1 polio
CD4 HIV
acetylcholine rabies
EGF vaccinia
CR2/CD21 Epstein-
Barr
HVEM herpes
Sialic acid Influenza,
reo, corona
Virus Replication
2) PENETRATION (Uptake)
• Is an energy-dependent process, i.
e. the cell must be metabolically
active for this to occur
• Endocytosis of the virus into
intracellular vacuoles
• Fusion of the viral envelope with
the cell membrane.
Fusion of viral envelope with Receptor-mediated endocytosis of
membrane of host cell. virus particle.
Virus Replication
3) UNCOATING
• The capsid is removed and the virus genome
is exposed
• Viruses which replicate in the cytoplasm, e.g.
Picornaviruses, the genome is released into
the cell
• Viruses which replicate in the nucleus, e.g.
Herpesviruses, the genome with
nucleoproteins, must be transported through
the nuclear membrane. At the nuclear pores,
the capsid is stripped off, and the genome
passes into the nucleus.
Virus Replication
4. EXPRESSION
Viral Nucleic Acid
Different viruses
Transcription use different
pathways
mRNA
Translation In general, DNA viruses
replicate mainly in the
nucleus and RNA viruses
Virus macromolecules mainly in the cytoplasm
• Structural Proteins
• Nonstructural Proteins
• Nucleic Acid
Virus Replication
Replication of DNA viruses.
assRNA genome
of (+) polarity replicates via a
complementary (–) strand intermediate.
an ssRNA genome
of (–) polarity that replicates via a
complementary (+) strand intermediate.
dsRNA genome.
ssRNA genome of (+)
polarity that replicates
via a DNA
intermediate.
Virus Replication
5) ASSEMBLY
• All the components necessary for the
formation of the mature virion
assemble
• The site of assembly varies e.g.
Cytoplasm: Picornaviruses, Poxviruses,
Reoviruses
Nucleus: Adenoviruses, Papovaviruses,
Parvoviruses
Inner surface of the cell membrane:
Virus Replication
6) RELEASE
a) Lysis of cell by lytic
viruses
b) Budding through cell
membrane as in
enveloped viruses
Release of enveloped virus from a
host cell by the process of “budding.”
Atypical Virus-like
Agents
Defective Viruses
• Are composed of viral nucleic acid and
proteins but cannot replicate without a
‘helper’ virus
• During growth many defective viruses are
produced in addition to infectious viruses
Pseudovirions
• Contain host cell DNA instead of viral DNA
within the capsid
• Can infect cells but do not replicate
43
Atypical Virus-like
Agents
Viroids
• Consist solely of a single molecule of circular RNA
without a protein coat or envelope
• RNA is small and does not code for any protein.
• Cause several plant diseases but are not implicated
in human diseases
Prions
• Are infectious particles that are composed solely of
protein and no detectable nucleic acid
• Are cause of certain slow diseases like Creutzfeldt-
Jacob Disease (CJD) in human and scrapie in sheep
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The summery
Viruses are the smallest infectious agents and contain only
one type of nucleic acid (DNA or RNA).
• Known viruses are highly diverse, varying in size, shape,
and genetic content; only some types possess a lipid
envelope.
• Viruses are classified into groups, designated virus
families,
based on common properties, such as virion morphology,
genome structure, virus protein properties, and strategies of
replication.
• Viruses are obligate intracellular parasites and multiply
only in living cells. The viral nucleic acid encodes virus
specific products, and the host cell provides energy,
biochemical precursors, and biosynthetic machinery.
• Steps in viral replication include attachment to a
cell via binding to specific receptors on the cell
surface, entry into the cell, uncoating of the viral
genome, regulated expression of viral transcripts,
synthesis of viral proteins, replication of viral
genomic nucleic acid, assembly of new progeny
viruses, and release of new virions from the cell.
The duration of replication cycles varies widely
among different virus types.
The infected cells may be killed or may survive
with little damage. Not all infections lead to new
progeny virus.
