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1
MEDICAL VIROLOGY
Assist Prof.Dr.Baydaa Hameed
2
VIRUSES CAN BE USEFUL
• VACCINE DEVELOPMENT
• GENE THERAPY
• TOOLS TO INVESTIGATE HOST
CELLS
3
CLASSIFICATION
• NUCLEIC ACID
• CAPSID
• PRESENCE OF ENVELOPE
• REPLICATION STRATEGY
4
• 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
CLASSIFICATION
NUCLEIC ACID
5
• symmetry
– icosahedral, helical, complex
• number of capsomers if icosahedral
• enveloped or non-enveloped
CLASSIFICATION
CAPSID
6
• viral genome properties:
– Type of nucleic acid (may be DNA or RNA).
– Molecular weight of nucleic acid.
– Number of strands (whether single strand or
double strand)of nucleic acid.
– Nucleic acid form(may be linear or circular ).
– Number and size of nucleic acid segments.
– Manner of replication.
:
Classification and
nomenclature of viruses
• Capsid properties including :
– Shape and size of viral particle.
– Number of capsomeres in capsid.
– Type of symmetry of nucleoprotein.
– Presence or absence of envelope.
– Presence or absence of spikes.
7
• Biological properties including:
– Susceptibility to physical and chemical
agents , especially ether and detergents ,
and stability to pH and temperature.
– Host specificity (natural host range).
– Mode of viral transmission.
– Organ specificity(tissue tropism) and
pathogenicity .
• 8
The nomenclature of viruses
• is not as in other organisms, but
classified into groupings which called
families, the family names have the
suffix-viridae . Each family , subdivided
into genera. The genus names carry
the suffix-virus.
9
The nomenclature of viruses
• Names of viruses are derived from:
• The name of disease caused by virus(eg:Influenza
virus, Hepatitis virus).
• The locality where the virus was first isolated (such
as ; West Nile virus).
• The name of scientists responsible for isolating
virus(such as; Epstein-Barr virus).
• Unique epidemiological characteristics of virus (such
as; Arboviruses, these are arthropod-borne viruses).
10
11
HERPESVIRIDAE
HEPADNAVIRIDAE
ENVELOPED
PAPILLOMAVIRIDAE
POLYOMAVIRIDAE
(formerly grouped together as the
PAPOVAVIRIDAE)
CIRCULAR
ADENOVIRIDAE
LINEAR
NON-ENVELOPED
DOUBLE STRANDED
PARVOVIRIDAE
SINGLE STRANDED
NON-ENVELOPED
POXVIRIDAE
COMPLEX
ENVELOPED
DNA VIRUSES
Modified from Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991
All families shown are
icosahedral except for
poxviruses
12
FLAVIVIRIDAE
TOGAVIRIDAE
RETROVIRIDAE
ICOSAHEDRAL
CORONAVIRIDAE
HELICAL
ENVELOPED
ICOSAHEDRAL
PICORNAVIRIDAE
CALICIVIRIDAE
ASTROVIRIDAE
NONENVELOPED
SINGLE STRANDED
positive sense
BUNYAVIRIDAE
ARENAVIRIDAE
ORTHOMYXOVIRIDAE
PARAMYXOVIRIDAE
RHABDOVIRIDAE
FILOVIRIDAE
SINGLE STRANDED
negative sense
REOVIRIDAE
DOUBLE STRANDED
RNA VIRUSES
ENVELOPED
HELICAL ICOSAHEDRAL
NONENVELOPED
Modified from Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991
13
BASIC STEPS IN VIRAL LIFE
CYCLE
• ADSORPTION
• PENETRATION
• UNCOATING AND ECLIPSE
• SYNTHESIS OF VIRAL NUCLEIC
ACID AND PROTEIN
• ASSEMBLY (maturation)
• RELEASE
14
ADSORPTION
15
ADSORPTION
• TEMPERATURE INDEPENDENT
• REQUIRES VIRAL ATTACHMENT
PROTEIN
• CELLULAR RECEPTORS
16
PENETRATION
- ENVELOPED VIRUSES
•FUSION WITH PLASMA MEMBRANE
•ENTRY VIA ENDOSOMES
17
PENETRATION
herpesviruses, paramyxoviruses, HIV
18
PENETRATION
- ENVELOPED VIRUSES
•FUSION WITH PLASMA MEMBRANE
•ENTRY VIA ENDOSOMES, FUSION
WITH ACIDIC ENDOSOME MEMBRANE
19
20
21
PENETRATION
- ENVELOPED VIRUSES
from Schaechter et al, Mechanisms of Microbial Disease, 3rd ed, 1998
22
VIRUS UPTAKE VIA
ENDOSOMES
• CALLED
– VIROPEXIS / ENDOCYTOSIS /
PINOCYTOSIS
23
PENETRATION
NON-ENVELOPED VIRUSES
entry directly across
plasma membrane:
24
25
UNCOATING
• NEED TO MAKE GENOME
AVAILABLE
• ONCE UNCOATING OCCURS, ENTER
ECLIPSE PHASE
• ECLIPSE PHASE LASTS UNTIL FIRST
NEW VIRUS PARTICLE FORMED
26
SYNTHESIS OF VIRAL
NUCLEIC ACID AND
PROTEIN
• MANY STRATEGIES
• NUCLEIC ACID MAY BE MADE IN
NUCLEUS OR CYTOPLASM
• PROTEIN SYNTHESIS IS ALWAYS IN
THE CYTOPLASM
27
ASSEMBLY AND
MATURATION
• NUCLEUS
• CYTOPLASM
• AT MEMBRANE
28
smallpox virus cytoplasmic assembly
and maturation
F. A. Murphy, School of Veterinary Medicine, University of California, Davis.
http://www.vetnet.ucdavis.edu/fam_graphics/download.html
29
RELEASE
• LYSIS
• BUDDING THROUGH PLASMA
MEMBRANE
• NOT EVERY RELEASED VIRION IS
INFECTIOUS
30
HIV budding and maturation
Hsiung, GD et al., Diagnostic Virology 1994 p204 (D. Medina)
• When a virus infects a cell, nucleic acid must be uncoated and gain
access to metabolic machinery of cell.
• Virus life cycle is characterized by:
– attachment
– penetration, with entry of nucleic acid into cell
– early expression of virus genes (either directly by translation, if virus
contains "+" RNA, or indirectly after transcription and then translation)
– replication of virus nucleic acid
– synthesis of new virion components
– packaging and assembly of new virions
– exit from cell
Viral Replication
• Attachment
– specific binding of a virion protein (the anti-receptor) to a
constituent of the cell surface (the receptor)
• e.g. hemagglutinin of influenza virus
• some complex viruses (HSV) may have more than one
species of anti-receptor molecule
• Penetration
– energy-dependent step
– occurs almost instantaneously after attachment
• After the virus attaches to the host cell, it can enter the cell by several
mechanisms:
– Transfer of the entire viral particle across the cell membrane by
endocytosis
– Transfer of only the viral genome through the cell membrane
– Fusion of the viral envelope with the host cell membrane
• Uncoating
– at same time as penetration or shortly after
– separation of viral nucleic acid (n.a.) from outer structural components
• Released as:
– free n.a. (picornaviruses)
– as nucleocapsid (reoviruses) = may need acidic pH in endosome
– viruses only infectious agent for which dissolution of infecting agent
obligatory step in replicative pathway
• Expression of viral genome and synthesis of viral components
• After the viral nucleic acid is released inside the host cell:
– The transcription and translation processes of the host cell are
redirected for the production of viral proteins and nucleic acids
– The different types of nucleic acid genomes are expressed and
replicated in several ways:
• DNA genomes undergo replication-using processes similar to
cellular replication
• RNA genomes may be +ssRNA; Can be read directly as an
mRNA or reverse transcribed by reverse transcriptase into
DNA
• RNA genomes may also be -ssRNA; The RNA must first be
used as a template to form +mRNAs
Assembly and Release
• Components of capsid synthesis directed by late genes
• Assembly of enveloped viruses needs interaction with plasma
membrane which has been modified
• Final stage of infection
• Enveloped viruses released gradually by budding or exocytosis
• Naked viruses accumulate in cytoplasm and released during
lysis
4_2018_03_08!03_32_30_PM.ppt 11111111111
4_2018_03_08!03_32_30_PM.ppt 11111111111

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4_2018_03_08!03_32_30_PM.ppt 11111111111

  • 2. 2 VIRUSES CAN BE USEFUL • VACCINE DEVELOPMENT • GENE THERAPY • TOOLS TO INVESTIGATE HOST CELLS
  • 3. 3 CLASSIFICATION • NUCLEIC ACID • CAPSID • PRESENCE OF ENVELOPE • REPLICATION STRATEGY
  • 4. 4 • 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 CLASSIFICATION NUCLEIC ACID
  • 5. 5 • symmetry – icosahedral, helical, complex • number of capsomers if icosahedral • enveloped or non-enveloped CLASSIFICATION CAPSID
  • 6. 6 • viral genome properties: – Type of nucleic acid (may be DNA or RNA). – Molecular weight of nucleic acid. – Number of strands (whether single strand or double strand)of nucleic acid. – Nucleic acid form(may be linear or circular ). – Number and size of nucleic acid segments. – Manner of replication. : Classification and nomenclature of viruses
  • 7. • Capsid properties including : – Shape and size of viral particle. – Number of capsomeres in capsid. – Type of symmetry of nucleoprotein. – Presence or absence of envelope. – Presence or absence of spikes. 7
  • 8. • Biological properties including: – Susceptibility to physical and chemical agents , especially ether and detergents , and stability to pH and temperature. – Host specificity (natural host range). – Mode of viral transmission. – Organ specificity(tissue tropism) and pathogenicity . • 8
  • 9. The nomenclature of viruses • is not as in other organisms, but classified into groupings which called families, the family names have the suffix-viridae . Each family , subdivided into genera. The genus names carry the suffix-virus. 9
  • 10. The nomenclature of viruses • Names of viruses are derived from: • The name of disease caused by virus(eg:Influenza virus, Hepatitis virus). • The locality where the virus was first isolated (such as ; West Nile virus). • The name of scientists responsible for isolating virus(such as; Epstein-Barr virus). • Unique epidemiological characteristics of virus (such as; Arboviruses, these are arthropod-borne viruses). 10
  • 11. 11 HERPESVIRIDAE HEPADNAVIRIDAE ENVELOPED PAPILLOMAVIRIDAE POLYOMAVIRIDAE (formerly grouped together as the PAPOVAVIRIDAE) CIRCULAR ADENOVIRIDAE LINEAR NON-ENVELOPED DOUBLE STRANDED PARVOVIRIDAE SINGLE STRANDED NON-ENVELOPED POXVIRIDAE COMPLEX ENVELOPED DNA VIRUSES Modified from Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991 All families shown are icosahedral except for poxviruses
  • 12. 12 FLAVIVIRIDAE TOGAVIRIDAE RETROVIRIDAE ICOSAHEDRAL CORONAVIRIDAE HELICAL ENVELOPED ICOSAHEDRAL PICORNAVIRIDAE CALICIVIRIDAE ASTROVIRIDAE NONENVELOPED SINGLE STRANDED positive sense BUNYAVIRIDAE ARENAVIRIDAE ORTHOMYXOVIRIDAE PARAMYXOVIRIDAE RHABDOVIRIDAE FILOVIRIDAE SINGLE STRANDED negative sense REOVIRIDAE DOUBLE STRANDED RNA VIRUSES ENVELOPED HELICAL ICOSAHEDRAL NONENVELOPED Modified from Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991
  • 13. 13 BASIC STEPS IN VIRAL LIFE CYCLE • ADSORPTION • PENETRATION • UNCOATING AND ECLIPSE • SYNTHESIS OF VIRAL NUCLEIC ACID AND PROTEIN • ASSEMBLY (maturation) • RELEASE
  • 15. 15 ADSORPTION • TEMPERATURE INDEPENDENT • REQUIRES VIRAL ATTACHMENT PROTEIN • CELLULAR RECEPTORS
  • 16. 16 PENETRATION - ENVELOPED VIRUSES •FUSION WITH PLASMA MEMBRANE •ENTRY VIA ENDOSOMES
  • 18. 18 PENETRATION - ENVELOPED VIRUSES •FUSION WITH PLASMA MEMBRANE •ENTRY VIA ENDOSOMES, FUSION WITH ACIDIC ENDOSOME MEMBRANE
  • 19. 19
  • 20. 20
  • 21. 21 PENETRATION - ENVELOPED VIRUSES from Schaechter et al, Mechanisms of Microbial Disease, 3rd ed, 1998
  • 22. 22 VIRUS UPTAKE VIA ENDOSOMES • CALLED – VIROPEXIS / ENDOCYTOSIS / PINOCYTOSIS
  • 24. 24
  • 25. 25 UNCOATING • NEED TO MAKE GENOME AVAILABLE • ONCE UNCOATING OCCURS, ENTER ECLIPSE PHASE • ECLIPSE PHASE LASTS UNTIL FIRST NEW VIRUS PARTICLE FORMED
  • 26. 26 SYNTHESIS OF VIRAL NUCLEIC ACID AND PROTEIN • MANY STRATEGIES • NUCLEIC ACID MAY BE MADE IN NUCLEUS OR CYTOPLASM • PROTEIN SYNTHESIS IS ALWAYS IN THE CYTOPLASM
  • 27. 27 ASSEMBLY AND MATURATION • NUCLEUS • CYTOPLASM • AT MEMBRANE
  • 28. 28 smallpox virus cytoplasmic assembly and maturation F. A. Murphy, School of Veterinary Medicine, University of California, Davis. http://www.vetnet.ucdavis.edu/fam_graphics/download.html
  • 29. 29 RELEASE • LYSIS • BUDDING THROUGH PLASMA MEMBRANE • NOT EVERY RELEASED VIRION IS INFECTIOUS
  • 30. 30 HIV budding and maturation Hsiung, GD et al., Diagnostic Virology 1994 p204 (D. Medina)
  • 31. • When a virus infects a cell, nucleic acid must be uncoated and gain access to metabolic machinery of cell. • Virus life cycle is characterized by: – attachment – penetration, with entry of nucleic acid into cell – early expression of virus genes (either directly by translation, if virus contains "+" RNA, or indirectly after transcription and then translation) – replication of virus nucleic acid – synthesis of new virion components – packaging and assembly of new virions – exit from cell Viral Replication
  • 32. • Attachment – specific binding of a virion protein (the anti-receptor) to a constituent of the cell surface (the receptor) • e.g. hemagglutinin of influenza virus • some complex viruses (HSV) may have more than one species of anti-receptor molecule • Penetration – energy-dependent step – occurs almost instantaneously after attachment
  • 33. • After the virus attaches to the host cell, it can enter the cell by several mechanisms: – Transfer of the entire viral particle across the cell membrane by endocytosis – Transfer of only the viral genome through the cell membrane – Fusion of the viral envelope with the host cell membrane
  • 34. • Uncoating – at same time as penetration or shortly after – separation of viral nucleic acid (n.a.) from outer structural components • Released as: – free n.a. (picornaviruses) – as nucleocapsid (reoviruses) = may need acidic pH in endosome – viruses only infectious agent for which dissolution of infecting agent obligatory step in replicative pathway • Expression of viral genome and synthesis of viral components
  • 35. • After the viral nucleic acid is released inside the host cell: – The transcription and translation processes of the host cell are redirected for the production of viral proteins and nucleic acids – The different types of nucleic acid genomes are expressed and replicated in several ways: • DNA genomes undergo replication-using processes similar to cellular replication • RNA genomes may be +ssRNA; Can be read directly as an mRNA or reverse transcribed by reverse transcriptase into DNA • RNA genomes may also be -ssRNA; The RNA must first be used as a template to form +mRNAs
  • 36. Assembly and Release • Components of capsid synthesis directed by late genes • Assembly of enveloped viruses needs interaction with plasma membrane which has been modified • Final stage of infection • Enveloped viruses released gradually by budding or exocytosis • Naked viruses accumulate in cytoplasm and released during lysis