Lect 1 introduction to medical virology

INTRODUCTION TO MEDICAL
VIROLOGY
(Structure, Classification & Replication)
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
• 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
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
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
• The virion contains an
elongated nucleocapsid
• The capsomeres are arranged
round the spiral of nucleic acid
• Most helical viruses are
enveloped
Viruses: Symmetry (Shapes)
Nucleic acid
Protein subunits
Viruses: Symmetry (Shapes)
• 3. Complex symmetry
• Does not conform to cubic
or helical symmetry
Lect 1 introduction to medical virology
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
Viruses: Classification
Viruses: Nomenclature
Family
(have the suffix –viridae)
e.g. Poxviridae
Genera
(have the suffix –virus)
e.g. Parvoviruses
Subfamilies
(in Poxvirinae, Herpesvirinae
Parvovirinae & paramyxovirinae)
Viruses in 24 families
infect humans & animals
Lect 1 introduction to medical virology
Lect 1 introduction to medical virology
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
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
Viral Replication
Viral Growth Curve
VirusReplication
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 37o
C
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.
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
Virus Replication
Viral Nucleic Acid
mRNA
Virus macromolecules
• Structural Proteins
• Nonstructural Proteins
• Nucleic Acid
Transcription
Translation
Different
viruses use
different
pathways
In general, DNA viruses
replicate mainly in the
nucleus and RNA viruses
mainly in the cytoplasm
VirusReplication
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: Retroviruses
Virus Replication
6) RELEASE
a) Lysis of cell by lytic
viruses
b) Budding through cell
membrane as in enveloped
viruses
Virus Replication
Differences Between Different Groups of Microorganisms
Growth on
artificial
media
Division by
binary
fission
Whether they
have both
DNA and
RNA
Whether they
have
ribosomes
Whether they
have
muramic ac
id
Their sensitivity
to
antibiotics
Bacteria Yes Yes Yes Yes Yes Yes
Mycoplasma Yes Yes Yes Yes No Yes
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
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
Atypical Virus-like
Agents
26
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
Atypical Virus-like
Agents
27
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Lect 1 introduction to medical virology

  • 1. INTRODUCTION TO MEDICAL VIROLOGY (Structure, Classification & Replication)
  • 2. 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
  • 3. • 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
  • 4. 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
  • 5. 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
  • 6. 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
  • 7. 1. Cubic Symmetry (Icosahedral) • Have exactly 60 subunits on the surface of an icosahedron • Have fivefold, threefold and twofold rotational symmetry Viruses: Symmetry (Shapes)
  • 8. 2. Helical Symmetry • The virion contains an elongated nucleocapsid • The capsomeres are arranged round the spiral of nucleic acid • Most helical viruses are enveloped Viruses: Symmetry (Shapes) Nucleic acid Protein subunits
  • 9. Viruses: Symmetry (Shapes) • 3. Complex symmetry • Does not conform to cubic or helical symmetry
  • 11. 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 Viruses: Classification
  • 12. Viruses: Nomenclature Family (have the suffix –viridae) e.g. Poxviridae Genera (have the suffix –virus) e.g. Parvoviruses Subfamilies (in Poxvirinae, Herpesvirinae Parvovirinae & paramyxovirinae) Viruses in 24 families infect humans & animals
  • 15. 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
  • 16. 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 Viral Replication Viral Growth Curve
  • 18. 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 37o C Virus Replication
  • 19. 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. Virus Replication
  • 20. 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
  • 21. 4. EXPRESSION Virus Replication Viral Nucleic Acid mRNA Virus macromolecules • Structural Proteins • Nonstructural Proteins • Nucleic Acid Transcription Translation Different viruses use different pathways In general, DNA viruses replicate mainly in the nucleus and RNA viruses mainly in the cytoplasm
  • 23. 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: Retroviruses Virus Replication
  • 24. 6) RELEASE a) Lysis of cell by lytic viruses b) Budding through cell membrane as in enveloped viruses Virus Replication
  • 25. Differences Between Different Groups of Microorganisms Growth on artificial media Division by binary fission Whether they have both DNA and RNA Whether they have ribosomes Whether they have muramic ac id Their sensitivity to antibiotics Bacteria Yes Yes Yes Yes Yes Yes Mycoplasma Yes Yes Yes Yes No Yes 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
  • 26. 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 Atypical Virus-like Agents 26
  • 27. 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 Atypical Virus-like Agents 27