VIRUSES
26/11/2014
Introduction
• Virology: study of structure, functions and
interactions of viruses with host
Viruses are not cells:
• Are not capable of reproducing independently
• Do not have a nucleus
• Do not have organelles such as ribosomes,
mitochondria and lysosomes
• Are smaller than cells
• Can not be seen in the light microscope
2
Evolutionary origin of viruses
• The origin is not known
Two theories of viral origin:
• Viruses may be derived from DNA and
RNA nucleic acid components of host
cells that became able to replicate
autonomously and evolve independently
–Some viral sequences are related to
portions of cellular genes encoding
protein functional domains
3
Evolutionary origin of viruses
• Viruses may be degenerate forms of
intracellular parasites
–No evidence that viruses evolved from
bacteria though other obligately
intracellular organisms e.g. rickettsiae,
chlamydiae presumably did so
–Poxviruses are so large and complex
that they represent evolutionary
products of some cellular ancestor
4
Definitions of Terms in used
Virology
• Viruses: Are smallest infectious agents (ranging from about
20 nm to about 300 nm in diameter) and contain only one kind
of nucleic acid (RNA or DNA) as their genome
• Capsid: The protein shell, or coat that encloses the nucleic
acid genome
• Capsomeres: Morphologic units of a capsid complete virion
• Nucleocapsid: The protein-nucleic acid complex plus a
capsid. Sometimes it is a complete virus particle
• The Virion:. In some instances the virion is identical with the
nucleocapsid. In more complex virion, it includes the
nucleocapsid plus a surrounding envelope
• Envelope: A lipid-containing membrane that surrounds some
virus particles
• Structural units: The basic protein building blocks of the
coat. They are usually a collection of more than one identical
protein subunit. The structural unit is often referred to as a
protomer
• Subunit: A single folded viral polypeptide chain
• Defective virus: A virus particle that is functionally deficient
in some aspect of replication
Characteristics of Viruses
• They are small in size ranging from about 20 nm to about 300
nm in diameter.
• They are akaryotic particles (neither eukaryotes nor
prokaryotes)
• They contain either DNA or RNA and not both as their
genome
• They exhibit living properties when inside the living cells (i.e.
they are incapable of independent reproduction unless they are
in the living cell)
• They are non motile
• They can be grown in cell cultures
• Viruses are known to infect unicellular organisms such as
mycoplasmas, bacteria, and algae and all higher plants and
animals
Generaly
• Viruses are particles composed of an
internal core containing either DNA or
RNA but not both, covered by a protective
protein coat
• Some viruses have an outer lipoprotein
membrane called an envelope external to
the coat
8
Generaly….
• Viruses must reproduce/replicate within
cells because they cannot generate
energy or synthesize proteins
• Because they can reproduce only within
cells viruses are obligate intracellular
parasites
• Viruses replicate in a manner different
from that of cells i.e. viruses do not
undergo binary fission or mitosis
9
Structure of Viruses
• Generally the virus structure is made of three basic units
o Envelop made of glycoprotein and lipids
o Capsid
o Viral core (RNA or DNA)
Parts of the Viral Structure and
its Function
Envelop
• Its function is to support glycoproteins or spikes used for
attachment to the host cell
• Gives stability to the virus
• Protects the inner parts of the virus
• It is usually derived from the host cell during release
(budding)
• Virus with an envelop are less stable than non enveloped virus
(they can be destroyed by disinfectants or adverse condition of
the environment)
Capsid
• Is a protein coat which covers the viral genome, it is made up
of repeating subunits called capsomers
• The repeating subunits of the capsid give the virus a
symmetric appearance that is useful for classification purposes
• Some viral nucleocapsids have spherical (icosahedral)
symmetry where as others have helical symmetry
• All human viruses that have a helical nucleocapsid are
enveloped (there are not naked helical viruses that infect
humans)
• Viruses that have an icosahedral nucleocapsid can be either
enveloped or naked
Viral Core
• Contains genetic materials necessary for replication.
They include either DNA or RNA, never both
• Deoxyribonucleic acid (DNA) containing viruses are
double stranded except parvoviruses which have
single strand DNA
• Ribonucleic Acid (RNA) containing viruses are
single stranded. Example human immunodeficiency
virus (HIV)
• Nucleic acid can either be linear or circular,
continuous or segmented
HOME WORK
•Classification of
viruses
Biology of Virus Replication
Introduction:
After infecting host cells, viruses redirect the
biochemical machinery of the host cell to produce
components for new virus particles by utilizing virus
mRNA
Production of mRNA is the most important
function of a virus and is the basic mechanism
for a virus to redirect host cell functions.
- In the laboratory, taking over of host cell
metabolism can be achieved by naked nucleic acid
alone free from viral capsid
- The capsid or outer coat of a virus protects viral
nucleic acid when virus is outside the cell.
Mechanisms utilized by virus in its replication
(i) Transcription
• Virus mRNA is made or utilized from the incoming
virus genome or nucleic acids as a template.
• This way information is transmitted from the virus
genome via virus mRNA to host cell ribosome where
proteins are synthesized.
(ii) Translation:
Virus mRNA attaches to host cell ribosomes and directs
formation of virus specific proteins:
- Early proteins – polymerases for new virus synthesis-RNA or
DNA
- Late proteins – catalysis for structural viral proteins for capsid
Virus specific Proteins:
(i) Structural proteins: - coded for by gag (core) and env
(envelope) genes.
These make up the capsid of the virus.
(i) Non-structural proteins – coded for by pol
(polymerase) genes.
Most are enzymes for processes of virus replication
esp. synthesis of new virus nucleic acids.
- The larger (bigger) the virus, the more the number of
non-structural proteins they code for.
Citrons: - Subunits of virus genome each of which contains
information for the production of one polypeptide
or protein.
Virus growth Cycle:
- Divided into stages
(i) Adsorption:
- Virus is adsorbed to specific receptors which may be
polypeptides or oligosaccharides on the cell plasma
membrane
- Adsorption is best at 37o
C but may also occur down to
4o
C but more slowly.
- Mg++ and Ca++ are enhancers of adsorption
- receptors on host cells which may number up to 105
per cell are fortuitous (occur by chance)
configurational homologies e.g.
for HIV found on CD4 molecules on T lymphocytes; for
rabies virus is acetylcholine while rhinoviruses bind on
ICAM-1 while Epstein Barr virus recognizes the CD21
receptors on B cells
Adsorption contd
- Presence or absence of receptors determines role in
cell tropism and viral pathogenesis e.g. polioviruses
are able to attach only on CNS and GIT receptors of
primates including man.
(ii) Entry (Penetration):
After adsorption cell membrane of host invaginates
(surrounds) the adsorbed particle best at 37o
C and not
at 4o
C in a process similar to phagocytosis or
engulfment or viropexis
(iii) Uncoating:
Removal of viral capsid by host cell enzymes
contained in lysosomes in order to release virus
nucleic acid into the host cell cytoplasm
(iv) Eclipse phase:
• Is the duration in hours in which no virus can be
recovered from the cell.
• It is the period when taking over of host cell
metabolism is happening.
(v) Synthesis of new viruses:
This takes place in the Nucleus of host cell by all
DNA viruses except Pox viruses while all RNA
viruses except Retroviridae and Orthomyxo
(Influenza) viruses replicate in the host cell
Cytoplasm.
(vi) Virus assembly:
Capsid + Nucleoproteins (RNA or DNA plus
surrounding proteins) are assembled to form new virus
particles
(vii) Virus release from host cells:
- If enveloped, part of envelope is added on during
release partly from host cell membrane.
Steps in synthesis of Viruses:
A. DNA viruses:
(i) Transcription – early mRNA from input DNA
(ii) Translation of early mRNA to early proteins (mainly
enzymes) for synthesis of progeny viral DNA
(iii) Transcription of progeny DNA to late mRNA
(IV) Translation of late mRNA to late structural
proteins (capsid and enzymes)– assembly –
release.
B. RNA viruses:
1.Input RNA may function as mRNA i.e. +ve strand e.g.
Polio virus which is directly translated to proteins
- RNA dependent RNA polymerases and structural
proteins formed
- Assembly – release
2. In put RNA for most enveloped RNA viruses e.g.
Influenza, Parainfluenza, Rabies, Mumps have –ve
strands and contain RNA dependent RNA
polymerase within the infectious particle
- Transcribes mRNA off in put parental or –ve strand
RNA.
-Replication then proceeds as for + stranded RNA
viruses
Viruses
Viruses
Viruses

Viruses

  • 1.
  • 2.
    Introduction • Virology: studyof structure, functions and interactions of viruses with host Viruses are not cells: • Are not capable of reproducing independently • Do not have a nucleus • Do not have organelles such as ribosomes, mitochondria and lysosomes • Are smaller than cells • Can not be seen in the light microscope 2
  • 3.
    Evolutionary origin ofviruses • The origin is not known Two theories of viral origin: • Viruses may be derived from DNA and RNA nucleic acid components of host cells that became able to replicate autonomously and evolve independently –Some viral sequences are related to portions of cellular genes encoding protein functional domains 3
  • 4.
    Evolutionary origin ofviruses • Viruses may be degenerate forms of intracellular parasites –No evidence that viruses evolved from bacteria though other obligately intracellular organisms e.g. rickettsiae, chlamydiae presumably did so –Poxviruses are so large and complex that they represent evolutionary products of some cellular ancestor 4
  • 5.
    Definitions of Termsin used Virology • Viruses: Are smallest infectious agents (ranging from about 20 nm to about 300 nm in diameter) and contain only one kind of nucleic acid (RNA or DNA) as their genome • Capsid: The protein shell, or coat that encloses the nucleic acid genome • Capsomeres: Morphologic units of a capsid complete virion • Nucleocapsid: The protein-nucleic acid complex plus a capsid. Sometimes it is a complete virus particle • The Virion:. In some instances the virion is identical with the nucleocapsid. In more complex virion, it includes the nucleocapsid plus a surrounding envelope
  • 6.
    • Envelope: Alipid-containing membrane that surrounds some virus particles • Structural units: The basic protein building blocks of the coat. They are usually a collection of more than one identical protein subunit. The structural unit is often referred to as a protomer • Subunit: A single folded viral polypeptide chain • Defective virus: A virus particle that is functionally deficient in some aspect of replication
  • 7.
    Characteristics of Viruses •They are small in size ranging from about 20 nm to about 300 nm in diameter. • They are akaryotic particles (neither eukaryotes nor prokaryotes) • They contain either DNA or RNA and not both as their genome • They exhibit living properties when inside the living cells (i.e. they are incapable of independent reproduction unless they are in the living cell) • They are non motile • They can be grown in cell cultures • Viruses are known to infect unicellular organisms such as mycoplasmas, bacteria, and algae and all higher plants and animals
  • 8.
    Generaly • Viruses areparticles composed of an internal core containing either DNA or RNA but not both, covered by a protective protein coat • Some viruses have an outer lipoprotein membrane called an envelope external to the coat 8
  • 9.
    Generaly…. • Viruses mustreproduce/replicate within cells because they cannot generate energy or synthesize proteins • Because they can reproduce only within cells viruses are obligate intracellular parasites • Viruses replicate in a manner different from that of cells i.e. viruses do not undergo binary fission or mitosis 9
  • 10.
    Structure of Viruses •Generally the virus structure is made of three basic units o Envelop made of glycoprotein and lipids o Capsid o Viral core (RNA or DNA)
  • 12.
    Parts of theViral Structure and its Function Envelop • Its function is to support glycoproteins or spikes used for attachment to the host cell • Gives stability to the virus • Protects the inner parts of the virus • It is usually derived from the host cell during release (budding) • Virus with an envelop are less stable than non enveloped virus (they can be destroyed by disinfectants or adverse condition of the environment)
  • 13.
    Capsid • Is aprotein coat which covers the viral genome, it is made up of repeating subunits called capsomers • The repeating subunits of the capsid give the virus a symmetric appearance that is useful for classification purposes • Some viral nucleocapsids have spherical (icosahedral) symmetry where as others have helical symmetry • All human viruses that have a helical nucleocapsid are enveloped (there are not naked helical viruses that infect humans) • Viruses that have an icosahedral nucleocapsid can be either enveloped or naked
  • 14.
    Viral Core • Containsgenetic materials necessary for replication. They include either DNA or RNA, never both • Deoxyribonucleic acid (DNA) containing viruses are double stranded except parvoviruses which have single strand DNA • Ribonucleic Acid (RNA) containing viruses are single stranded. Example human immunodeficiency virus (HIV) • Nucleic acid can either be linear or circular, continuous or segmented
  • 15.
  • 16.
    Biology of VirusReplication Introduction: After infecting host cells, viruses redirect the biochemical machinery of the host cell to produce components for new virus particles by utilizing virus mRNA Production of mRNA is the most important function of a virus and is the basic mechanism for a virus to redirect host cell functions. - In the laboratory, taking over of host cell metabolism can be achieved by naked nucleic acid alone free from viral capsid - The capsid or outer coat of a virus protects viral nucleic acid when virus is outside the cell.
  • 17.
    Mechanisms utilized byvirus in its replication (i) Transcription • Virus mRNA is made or utilized from the incoming virus genome or nucleic acids as a template. • This way information is transmitted from the virus genome via virus mRNA to host cell ribosome where proteins are synthesized. (ii) Translation: Virus mRNA attaches to host cell ribosomes and directs formation of virus specific proteins: - Early proteins – polymerases for new virus synthesis-RNA or DNA - Late proteins – catalysis for structural viral proteins for capsid
  • 18.
    Virus specific Proteins: (i)Structural proteins: - coded for by gag (core) and env (envelope) genes. These make up the capsid of the virus. (i) Non-structural proteins – coded for by pol (polymerase) genes. Most are enzymes for processes of virus replication esp. synthesis of new virus nucleic acids. - The larger (bigger) the virus, the more the number of non-structural proteins they code for. Citrons: - Subunits of virus genome each of which contains information for the production of one polypeptide or protein.
  • 19.
    Virus growth Cycle: -Divided into stages (i) Adsorption: - Virus is adsorbed to specific receptors which may be polypeptides or oligosaccharides on the cell plasma membrane - Adsorption is best at 37o C but may also occur down to 4o C but more slowly. - Mg++ and Ca++ are enhancers of adsorption - receptors on host cells which may number up to 105 per cell are fortuitous (occur by chance) configurational homologies e.g. for HIV found on CD4 molecules on T lymphocytes; for rabies virus is acetylcholine while rhinoviruses bind on ICAM-1 while Epstein Barr virus recognizes the CD21 receptors on B cells
  • 20.
    Adsorption contd - Presenceor absence of receptors determines role in cell tropism and viral pathogenesis e.g. polioviruses are able to attach only on CNS and GIT receptors of primates including man. (ii) Entry (Penetration): After adsorption cell membrane of host invaginates (surrounds) the adsorbed particle best at 37o C and not at 4o C in a process similar to phagocytosis or engulfment or viropexis (iii) Uncoating: Removal of viral capsid by host cell enzymes contained in lysosomes in order to release virus nucleic acid into the host cell cytoplasm
  • 21.
    (iv) Eclipse phase: •Is the duration in hours in which no virus can be recovered from the cell. • It is the period when taking over of host cell metabolism is happening. (v) Synthesis of new viruses: This takes place in the Nucleus of host cell by all DNA viruses except Pox viruses while all RNA viruses except Retroviridae and Orthomyxo (Influenza) viruses replicate in the host cell Cytoplasm. (vi) Virus assembly: Capsid + Nucleoproteins (RNA or DNA plus surrounding proteins) are assembled to form new virus particles (vii) Virus release from host cells: - If enveloped, part of envelope is added on during release partly from host cell membrane.
  • 22.
    Steps in synthesisof Viruses: A. DNA viruses: (i) Transcription – early mRNA from input DNA (ii) Translation of early mRNA to early proteins (mainly enzymes) for synthesis of progeny viral DNA (iii) Transcription of progeny DNA to late mRNA (IV) Translation of late mRNA to late structural proteins (capsid and enzymes)– assembly – release. B. RNA viruses: 1.Input RNA may function as mRNA i.e. +ve strand e.g. Polio virus which is directly translated to proteins - RNA dependent RNA polymerases and structural proteins formed - Assembly – release
  • 23.
    2. In putRNA for most enveloped RNA viruses e.g. Influenza, Parainfluenza, Rabies, Mumps have –ve strands and contain RNA dependent RNA polymerase within the infectious particle - Transcribes mRNA off in put parental or –ve strand RNA. -Replication then proceeds as for + stranded RNA viruses