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Virology Prions
Introduction
• Viruses are the smallest, subcellular agents that are unable to
replicate outside host’s cell.
General properties:-
 Viruses are not cell, they do not have a nucleus, cytoplasm,
mitochondria, or ribosomes
They contain one kind of nucleic acid (RNA or DNA) covered
by protective protein coat (known as capsid).
 Some viruses have outer lipoprotein membrane (called envelope).
They are obligate intracellular parasites, because they can’t generate
their energy or proteins.
They do not undergo binary fission or mitosis.
Property Virus Cell
Type of nucleic acid DNA or RNA DNA and RNA
Proteins Few Many
Ribosomes Absent Present
Multiplication by binary
fission or mitosis
No Yes
Comparison between viruses and cells
Viral structure
 Viruses are consist of two or three major components:
1. Nucleic acids (DNA or RNA).
2. Capsid (protein coat).
3. Envelope (lipoprotein)(exist in some viruses).
Note:
 Viruses have no envelope known as naked.
Viral nucleic acids (genome):
• The viral genome is located internally.
• The nucleic acid of a virus may occur in various forms.
1. It may be composed of DNA or RNA.
2. It can either be single-stranded or double-stranded.
3. The nucleic acid may occur as a continuous molecule, or it
may be segmented.
Viral capsid
 Its a protein coat covered the genome.
 It is made up of subunits known as capsomers.
 Capsomer is consist of single or several proteins.
• Nucleic acid + Capsid Nucleocapsid
• The arrangement of capsomers gives the virus its geometric symmetry.
Viral symmetry:-
• Viral nucleocapsids have three forms of symmetry
1. Icosahedral, in which the capsomers are arranged in 20 triangles
(icosahedron).
• The viruses that cause chickenpox and flaccid (soft) paralysis have
icosahedral symmetry
2. Helical, in which the capsomers are arranged in a cavity coil that
appears like rod-shaped (influenza virus).
• There are some viruses that have neither icosahedral nor helical
symmetry such as smallpox and Bacteriophage. These viruses have
symmetry known as complex symmetry.
Bacteriophage
Function of the capsid: ‫طالب‬
Protect the viral genetic material.
1. Mediate the attachment of the virus to specific receptors on the
host cell surface (organ specificity).
2. They can induce antibody and cytotoxic T cells response.
Viral envelope:-
• It is a lipoprotein membrane composed of lipid derived from the
host cell membrane and protein that is virus-specific.
• The viral envelope is acquired as the virus exits from the cell in a
process called budding.
Classification of medically important viruses ‫طالبات‬
 Criteria used for viruses classification:
I. Virion morphology, including:
 Size
 Type of symmetry
 Presence or absence of envelope.
II. Viral genome properties:
 Type of nucleic acid (DNA or RNA)
 Strandedness (ss or ds)
 Whether linear or circular, sense (positive, negative)
III. Physicochemical properties of the virion, including
susceptibility to physical and chemical agents.
IV. Biologic properties, including natural host range, mode of
transmission, tissue tropisms, and pathology.
 Viruses are separated into major groups—called families:
 Family–viridae
Subfamily –virinae
DNA viruses
The medically DNA viruses are classified into 7 families:
1. Four naked icoshedral viruses families:-
 Parvoviridae
 Polyomaviridae
 Papillomaviridae
 Adenoviridae
2. Three enveloped families:-
 Hepadanviridae
 Herpesviridae
 Poxviridae
RNA viruses
 There are 14 families of RNA viruses:
1. Three naked icosahedral viruses families
• Picornaviridae
• Caliciviridae
• Reoviridae.
2. Three enveloped icosahedral viruses families
• Flaviviridae
• Togaviridae
• Retroviridae.
3. Eight enveloped helical viruses:
• Orthomyxoviridae
• Paramyxoviridae
• Rhabdoviridae
• Filoviridae
• Coronaviridae
• Arenaviridae
• Bunyaviridae
• Deltaviridae
Viral replication
Virus replicates only inside living cell.
Virus doesn’t reproduce by binary fission or mitosis.
One virion infects a cell, it can reproduce into hundreds of virions.
1. Attachment and penetration
2. Uncoating of the viral genome
3. Genome replication & expression
4. Progeny virion assembly
5. Virion release from cell
Stepwise of viral replication
1. Attachment and penetration:
• Viral capsid or glycoprotein bind to specific receptor proteins
on the host cell surface through noncovalent bonding.
• After binding, the virus nucleocapsid is taken up inside the cell
by endocytosis.
2. Uncoating:
• After penetration, the viral nucleic acid physically separated from
the capsid.
3. Genome replication and expression:
• DNA viruses replicate in the nucleus.
• RNA viruses replicate in the cytoplasm.
• The first step gene expression is mRNA synthesis and then,
translation it into proteins.
4. Assembly:
• Assembly is packaging of the viral nucleic acid within the capsid
proteins.
5. Virion release from cell
• Virus particles are released from the cell by either of two
processes;
1. By rupture of the cell membrane and release of the mature
particles (naked viruses).
2. By budding through the outer cell membrane or nuclear
membrane (enveloped viruses).
Stepwise of viral replication
Stepwise of viral pathogenesis:-
1. Transmission of the virus and its portal of entry into the host.
2. Replication of the virus and damage of the cells.
3. Spread of the virus between host cells and organs.
4. The immune response, both as a host defense and as a
contributing in causing of diseases.
5. Persistence of the virus infection.
Viral pathogenesis
Transmission and portal of entry:
 Person-to-person (Horizontal transmission) by respiratory
aerosol, saliva, blood, or semen.
 Fecal-oral route.
 Transmission of virus between mother and offspring (vertical
transmission)
Animal-to-human transmission (zoonotic) (e.g., rabies, yellow
fever virus, dengue virus etc).
Portals of exit:
• Respiratory tract
• Coughing and sneezing: respiratory diseases microbes
• Gastrointestinal tract
• Feces and saliva: Salmonellosis, Cholera
• Genitourinary tract
• Urine and vaginal secretions: STMs, Typhoid fever
• Skin
• Squames shed into atmosphere: impetigo, Herpes
• Blood
• Biting arthropods and needles or syringes: Malaria, HIV
Cytopathic effects of viruses:
 Effects of virus infection on appearance of
host cells include:
• Cell lysis
• Formation of inclusion bodies – viral
particles under assembly (use for diagnosis:
eg. rabies, measles, smallpox)
• Syncytium formation – a fusion of adjacent
cells (e.g. measles, the common cold)
 Determination of cytopathic effect in
laboratory cell lines is used in diagnosis of viral
infections
Inclusion bodies are found in the cytoplasm
or nucleus of some infected cells.
Localization or disseminated infection
 Viral infections are either localized at the portal of entry
or spread to another organ (systemic).
1. Localized infection:
• Rhinoviruses cause common cold, which involves only
the upper respiratory tract.
2. Systemic infection (disseminated ):
• Poliovirus cause poliomyelitis
Immunopathogenesis:
• Immune system attacks viral infected cells causing tissue damage
and loss of function.
Example pathogenesis of hepatitis caused by hepatitis A, B, and C
viruses.
 The skin rash caused measles virus.
 Arthritis seen in hepatitis B, parvovirus B19 and rubella virus.
Persistent Infection:-
• Certain viruses can persist for long periods either intact or in the
form of subviral component (genome).
• Viruses established persistent infections by one of the following
mechanisms:
1. Integration of a DNA provirus into host cell DNA (e.g.,
retroviruses).
2. Immune tolerance (unresponsiveness).
3. Rapid antigenic variation
Types of persistent infection:
• There are 3 types of persistent infection.
1. Chronic carrier infection:
• Carrier state refers to asymptomatic people who produce virus for
long periods of time and can serve as a source of infection for others
(e.g., HBV & HCV).
2. Latent infections:
• Those infections that are not producing virus at the present time but
can be reactivated at a subsequent time (e.g., herpesviruses).
3. Slow virus infections:
• The term "slow" refers to the prolonged period between the initial
infection and the onset of disease (progressive multifocal
leukoencephalopathy caused JC virus).
• Prions are very small proteinaceous units that cause Transmissible Spongiform
Encephalopathies (TSEs) when folded abnormally.
• Abnormally folded prions can cause fatal neurodegenerative disease (particularly in the brain) by
converting normally folded prions into abnormal ones.
• Prion diseases, are characterized by long incubation periods, spongiform changes in the brain,
and a failure to induce an inflammatory response.
• The most common form of prion disease in humans is Creutzfeldt-Jakob disease (CJD).
• Prion diseases are rare, untreatable, and fatal, with symptoms that reflect the destruction of the
brain, including memory loss and difficulties with movement.
• Risk factors for prion disease include a family history of the disease and consumption of meat
infected by "mad cow disease"
Prions:
• Abnormal, pathogenic agents that are transmissible and are able to
induce abnormal folding of specific normal cellular proteins called
prion proteins that are found most abundantly in the brain.
Cleaning: Prions are difficult to remove from reusable medical devices
due to their small size and their strong adherence to surfaces.
• They are very difficult to inactivate using heat or disinfectants.
• Reusable medical devices used on prion-infected patient tissues are
not used on other patients due to difficulty in decontaminating them.
• It is important to have a traceability system for medical devices in
place to ensure these reusable medical devices are not used again.
Identification: Prions are usually detected by histopathology of infected
tissue where misfolded prion aggregates are revealed using specific
antibodies linked to dyes.
• Detection on reusable medical devices is very complex and time
consuming and is not very successful.
Other prion-like agents: Not much is known about these yet other than
they are very small molecules and are transmissible.
• They have effects similar to prions and are thought to be equally
difficult to inactivate.
Thank You

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9- Introduction to Virology and Prions.pptx

  • 2. Introduction • Viruses are the smallest, subcellular agents that are unable to replicate outside host’s cell. General properties:-  Viruses are not cell, they do not have a nucleus, cytoplasm, mitochondria, or ribosomes They contain one kind of nucleic acid (RNA or DNA) covered by protective protein coat (known as capsid).  Some viruses have outer lipoprotein membrane (called envelope).
  • 3. They are obligate intracellular parasites, because they can’t generate their energy or proteins. They do not undergo binary fission or mitosis. Property Virus Cell Type of nucleic acid DNA or RNA DNA and RNA Proteins Few Many Ribosomes Absent Present Multiplication by binary fission or mitosis No Yes Comparison between viruses and cells
  • 4. Viral structure  Viruses are consist of two or three major components: 1. Nucleic acids (DNA or RNA). 2. Capsid (protein coat). 3. Envelope (lipoprotein)(exist in some viruses). Note:  Viruses have no envelope known as naked.
  • 5. Viral nucleic acids (genome): • The viral genome is located internally. • The nucleic acid of a virus may occur in various forms. 1. It may be composed of DNA or RNA. 2. It can either be single-stranded or double-stranded. 3. The nucleic acid may occur as a continuous molecule, or it may be segmented.
  • 6. Viral capsid  Its a protein coat covered the genome.  It is made up of subunits known as capsomers.  Capsomer is consist of single or several proteins. • Nucleic acid + Capsid Nucleocapsid • The arrangement of capsomers gives the virus its geometric symmetry.
  • 7. Viral symmetry:- • Viral nucleocapsids have three forms of symmetry 1. Icosahedral, in which the capsomers are arranged in 20 triangles (icosahedron). • The viruses that cause chickenpox and flaccid (soft) paralysis have icosahedral symmetry
  • 8. 2. Helical, in which the capsomers are arranged in a cavity coil that appears like rod-shaped (influenza virus).
  • 9. • There are some viruses that have neither icosahedral nor helical symmetry such as smallpox and Bacteriophage. These viruses have symmetry known as complex symmetry. Bacteriophage
  • 10. Function of the capsid: ‫طالب‬ Protect the viral genetic material. 1. Mediate the attachment of the virus to specific receptors on the host cell surface (organ specificity). 2. They can induce antibody and cytotoxic T cells response.
  • 11. Viral envelope:- • It is a lipoprotein membrane composed of lipid derived from the host cell membrane and protein that is virus-specific. • The viral envelope is acquired as the virus exits from the cell in a process called budding.
  • 12. Classification of medically important viruses ‫طالبات‬  Criteria used for viruses classification: I. Virion morphology, including:  Size  Type of symmetry  Presence or absence of envelope. II. Viral genome properties:  Type of nucleic acid (DNA or RNA)  Strandedness (ss or ds)  Whether linear or circular, sense (positive, negative)
  • 13. III. Physicochemical properties of the virion, including susceptibility to physical and chemical agents. IV. Biologic properties, including natural host range, mode of transmission, tissue tropisms, and pathology.  Viruses are separated into major groups—called families:  Family–viridae Subfamily –virinae
  • 14. DNA viruses The medically DNA viruses are classified into 7 families: 1. Four naked icoshedral viruses families:-  Parvoviridae  Polyomaviridae  Papillomaviridae  Adenoviridae 2. Three enveloped families:-  Hepadanviridae  Herpesviridae  Poxviridae
  • 15. RNA viruses  There are 14 families of RNA viruses: 1. Three naked icosahedral viruses families • Picornaviridae • Caliciviridae • Reoviridae. 2. Three enveloped icosahedral viruses families • Flaviviridae • Togaviridae • Retroviridae.
  • 16. 3. Eight enveloped helical viruses: • Orthomyxoviridae • Paramyxoviridae • Rhabdoviridae • Filoviridae • Coronaviridae • Arenaviridae • Bunyaviridae • Deltaviridae
  • 17.
  • 18. Viral replication Virus replicates only inside living cell. Virus doesn’t reproduce by binary fission or mitosis. One virion infects a cell, it can reproduce into hundreds of virions.
  • 19. 1. Attachment and penetration 2. Uncoating of the viral genome 3. Genome replication & expression 4. Progeny virion assembly 5. Virion release from cell Stepwise of viral replication
  • 20. 1. Attachment and penetration: • Viral capsid or glycoprotein bind to specific receptor proteins on the host cell surface through noncovalent bonding. • After binding, the virus nucleocapsid is taken up inside the cell by endocytosis. 2. Uncoating: • After penetration, the viral nucleic acid physically separated from the capsid.
  • 21. 3. Genome replication and expression: • DNA viruses replicate in the nucleus. • RNA viruses replicate in the cytoplasm. • The first step gene expression is mRNA synthesis and then, translation it into proteins. 4. Assembly: • Assembly is packaging of the viral nucleic acid within the capsid proteins.
  • 22. 5. Virion release from cell • Virus particles are released from the cell by either of two processes; 1. By rupture of the cell membrane and release of the mature particles (naked viruses). 2. By budding through the outer cell membrane or nuclear membrane (enveloped viruses).
  • 23. Stepwise of viral replication
  • 24. Stepwise of viral pathogenesis:- 1. Transmission of the virus and its portal of entry into the host. 2. Replication of the virus and damage of the cells. 3. Spread of the virus between host cells and organs. 4. The immune response, both as a host defense and as a contributing in causing of diseases. 5. Persistence of the virus infection. Viral pathogenesis
  • 25. Transmission and portal of entry:  Person-to-person (Horizontal transmission) by respiratory aerosol, saliva, blood, or semen.  Fecal-oral route.  Transmission of virus between mother and offspring (vertical transmission) Animal-to-human transmission (zoonotic) (e.g., rabies, yellow fever virus, dengue virus etc).
  • 26. Portals of exit: • Respiratory tract • Coughing and sneezing: respiratory diseases microbes • Gastrointestinal tract • Feces and saliva: Salmonellosis, Cholera • Genitourinary tract • Urine and vaginal secretions: STMs, Typhoid fever • Skin • Squames shed into atmosphere: impetigo, Herpes • Blood • Biting arthropods and needles or syringes: Malaria, HIV
  • 27. Cytopathic effects of viruses:  Effects of virus infection on appearance of host cells include: • Cell lysis • Formation of inclusion bodies – viral particles under assembly (use for diagnosis: eg. rabies, measles, smallpox) • Syncytium formation – a fusion of adjacent cells (e.g. measles, the common cold)  Determination of cytopathic effect in laboratory cell lines is used in diagnosis of viral infections Inclusion bodies are found in the cytoplasm or nucleus of some infected cells.
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  • 31. Localization or disseminated infection  Viral infections are either localized at the portal of entry or spread to another organ (systemic). 1. Localized infection: • Rhinoviruses cause common cold, which involves only the upper respiratory tract. 2. Systemic infection (disseminated ): • Poliovirus cause poliomyelitis
  • 32.
  • 33. Immunopathogenesis: • Immune system attacks viral infected cells causing tissue damage and loss of function. Example pathogenesis of hepatitis caused by hepatitis A, B, and C viruses.  The skin rash caused measles virus.  Arthritis seen in hepatitis B, parvovirus B19 and rubella virus.
  • 34. Persistent Infection:- • Certain viruses can persist for long periods either intact or in the form of subviral component (genome). • Viruses established persistent infections by one of the following mechanisms: 1. Integration of a DNA provirus into host cell DNA (e.g., retroviruses). 2. Immune tolerance (unresponsiveness). 3. Rapid antigenic variation
  • 35. Types of persistent infection: • There are 3 types of persistent infection. 1. Chronic carrier infection: • Carrier state refers to asymptomatic people who produce virus for long periods of time and can serve as a source of infection for others (e.g., HBV & HCV).
  • 36. 2. Latent infections: • Those infections that are not producing virus at the present time but can be reactivated at a subsequent time (e.g., herpesviruses). 3. Slow virus infections: • The term "slow" refers to the prolonged period between the initial infection and the onset of disease (progressive multifocal leukoencephalopathy caused JC virus).
  • 37. • Prions are very small proteinaceous units that cause Transmissible Spongiform Encephalopathies (TSEs) when folded abnormally. • Abnormally folded prions can cause fatal neurodegenerative disease (particularly in the brain) by converting normally folded prions into abnormal ones. • Prion diseases, are characterized by long incubation periods, spongiform changes in the brain, and a failure to induce an inflammatory response. • The most common form of prion disease in humans is Creutzfeldt-Jakob disease (CJD). • Prion diseases are rare, untreatable, and fatal, with symptoms that reflect the destruction of the brain, including memory loss and difficulties with movement. • Risk factors for prion disease include a family history of the disease and consumption of meat infected by "mad cow disease" Prions: • Abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain.
  • 38. Cleaning: Prions are difficult to remove from reusable medical devices due to their small size and their strong adherence to surfaces. • They are very difficult to inactivate using heat or disinfectants. • Reusable medical devices used on prion-infected patient tissues are not used on other patients due to difficulty in decontaminating them. • It is important to have a traceability system for medical devices in place to ensure these reusable medical devices are not used again. Identification: Prions are usually detected by histopathology of infected tissue where misfolded prion aggregates are revealed using specific antibodies linked to dyes. • Detection on reusable medical devices is very complex and time consuming and is not very successful. Other prion-like agents: Not much is known about these yet other than they are very small molecules and are transmissible. • They have effects similar to prions and are thought to be equally difficult to inactivate. Thank You

Editor's Notes

  1. A prion is a type of protein that can trigger normal proteins in the brain to fold abnormally. Prion diseases can affect both humans and animals and are sometimes spread to humans by infected meat products.  Creutzfeldt-Jakob disease (CJD) is a rare, rapidly worsening brain disorder that causes unique changes in brain tissue and affects muscle coordination thinking, and memory.