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By: Dr. Malak El-Hazmi
Dr. Abdulkarim Alhetheel
Introduction to medical virology Introduction to medical virology ““Viral Pathogenesis”Viral Pathogenesis”
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OBJECTIVESOBJECTIVES
• Definition and levels of viral pathogenesis.• Types of viral infections at cellular level.
• Pathogenesis at host level.• The immune response to viral infection.
• The stages of viral infection.• The types of viral infections at host level.
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Viral disease at the cellular level
Cytopathogenesis
Viral disease at the host level
Mechanism of the disease
PathogenesisPathogenesis of viral infection of viral infection
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Abortive Vs not produced Productive
Cytolytic Vs Produced Non-cytolytic Vs Produced
[Persistant] Non-productive Vs not Produced
Latent [ Pt ] Viral NA present
Transformation [ Pt ] Viral NA present
Cytopathogenesis: Cytopathogenesis: The types of viral infections at cellular levelThe types of viral infections at cellular level
The effects on cells/ Type of Infection
Virus Production
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AA) ) Abortive Infections:Abortive Infections: Viruses don’t complete
the replication cycle Due to mutation,
defective interfering particles
& the action of IFNs
BB)) Productive Infections:Productive Infections: 1. Cytolytic Infections
Viruses replicate
& produce progeny Cell death & Cytopathic effects [CPE] Inhibition of cellular protein & NA synthesis
The types of viral infections at The types of viral infections at cellular levelcellular level
AA
BB
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CPE can take several forms: 1. Cell lysis
2. Cell rounding
3. Syncytium formation
4. Inclusion bodies formation
Cytopathic Effects Cytopathic Effects
Uninfected cc Cell rounding Cyncytium
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Syncytium formation Syncytium formation
Cc ;Syncytium (RSV)
HerpesparamyxoVs
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Site: Intranuclear [Herpes] Intracytoplasmic [Rabies]
Take several forms:
Single/multiple Small/large Round/irregular
Inclusion bodies formationInclusion bodies formation
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Negri bodies caused
by Rabies virus
Owl’s eye inclusions caused by CMV
Inclusion bodies Inclusion bodies formationformation
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BB) Productive Infections:Productive Infections:
1. Cytolytic Infections 1. Cytolytic Infections
2. Non-cytolytic infections 2. Non-cytolytic infections :: Viruses replicate & produce progeny Vs released by cell budding & little or no CPE Identified by hemadsorption & direct IF
The types of viral infections at The types of viral infections at cellular levelcellular level
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CC) Non-productive Infections:Non-productive Infections: Vs infect cells that restrict or lack the machinery for
transcribing viral genes. Viral genome is found either integrated into cell
DNA or as a circular episome or both.
1)1) Latent Infection:Latent Infection: Persistent infection b/c
there is limited expression of viral genes The cell retains its normal properties Ex: HSV
The types of viral infections at The types of viral infections at cellular levelcellular level
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2) 2) Transformation:Transformation:
Ex ; EBV, HPV and HTLV Cause tumor in animals & H
and can transform cell culture
Vs can stimulate uncontrolled cell growth causing Tf by alternating the balance between growth activators &growth suppressors gene products
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Abortive Vs not produced Productive
Cytolytic Vs Produced Non-cytolytic Vs Produced
[Persistant] Non-productive Vs not Produced
Latent [ Pt ] Viral NA present
Transformation [ Pt ] Viral NA present
Cytopathogenesis: Cytopathogenesis: The types of viral infections at cellular levelThe types of viral infections at cellular level
The effects on cells/ Type of Infection
Virus Production
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1. Transmission of the virus & its entry into the host.2. Replication of the virus & damage to cells3. Vs remain localized or spread to other organs 4. Viral shedding
5. The immune response as
Host defense Immunopathogenesis
Pathogenesis at Pathogenesis at Host LevelHost Level
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1.1. Person to personPerson to person a) Horizontal transmission
Skin contact , Blood Respiratory route Fecal - oral route Genital contact
b) Vertical transmission
2.2. Animal to personAnimal to person
TransmissionTransmission
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Route of Entry Virus Disease (L/G)
Skin
Mild Trauma HPV Warts (L)
Injection (Blood) HBV,HCV, HIV Hepatitis B, Hepatitis C ,AIDS (G)
Bite of insect animal
Yellow fever virus Rabies virus
Yellow fever (G)Rabies (G)
Respiratory tract HSV-1RhinovirusRSVAdenovirusVZVMeasles virus
Gingivostomatitis (L) (URT) Common cold (L) (URT)Bronchiolitis (L) (LRT)Pneumonia (L) (LRT)Chickenpox (G)Measles (G)
GIT Rotavirus HAVPoliovirus
Diarrhea (L)Hepatitis A (G)Poliomyelitis (G)
Genital tract HSV-2
HBVHIV
Genital herpes (L)Meningitis (G)Encephalitis (G)Hepatitis B (G)AIDS(G)
Common Routes of Human Infection by Viruses Common Routes of Human Infection by Viruses
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Mechanisms of spread of virus Mechanisms of spread of virus through the bodythrough the body
Virus Virus sheddingshedding
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Important features of Acute Viral DiseasesImportant features of Acute Viral Diseases
Local Infections Systemic Infections
Ex. of specific Disease Rhinovirus Measles
Site of Pathology Portal of entry Distant site
IP Relatively short Relatively long
Viremia Absent Present
Duration of Immunity Variable- may be short Usually life long
Role of Secretory AB [IgA]
in resistance
Usually important Usually not important
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The immune response The immune response to virusto virus
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CCytokinesytokines:: Interferons (IFN)
α , β IFN inhibit the viral and the host cell mRNA translation
γ IFN stimulate phagocytosis and killing by macrophage & NK cells
Interleukin (IL) Stimulate AB production Activate T cells & CMI Suppress the IR
The immune response to The immune response to
virusvirus
MMacrophagesacrophages:: APC, Phagocytosis, Cytokines production
Natural killer (Natural killer (NKNK) cells) cells : : Lysis of VICs
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The immune response The immune response to virusto virus
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CMI:CMI: Effective against intracellular viruses Lysis of virally infected cells by CTCs [CD8]
Humoral Immunity:Humoral Immunity: Effective on extracellular viruses [viremia] - Neutralization
The immune response to The immune response to virusvirus
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1. The incubation period 2. Prodromal period3. The specific-illness period:
The signs & symptoms of viral diseases are the result of Cell killing by:
A) Inhibition of cellular macromolecular synthesis B) Immunologic attack ( Immunopathogenesis)
Cytotoxic T cells e.g. Hepatitis (HAV, HBV,HCV)
4. The recovery period
The stages of a typical viral infection:The stages of a typical viral infection:
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1. Asymptomatic infection
2. Acute infection
3. Persistent infection Late complication
of acute infection Latent infection Chronic infection
Types of viral infections at host level:Types of viral infections at host level:
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Reference books Reference books &the relevant page numbers&the relevant page numbers
Medical Microbiology and Immunology Medical Microbiology and Immunology
By: Warren Levinson .By: Warren Levinson .
1010thth Edition, 2008. Edition, 2008.
Pages;221-232Pages;221-232 Medical Microbiology.Medical Microbiology.
By: By: David Greenwood ,Richard C.B. SlackDavid Greenwood ,Richard C.B. Slack
John F Peutherer and Mike Barer.John F Peutherer and Mike Barer.
1717thth Edition, 2007. Edition, 2007.
Pages;80,90-92Pages;80,90-92 Lippincott’s Illustrated Reviews: Microbiology Lippincott’s Illustrated Reviews: Microbiology
By: William A. Strohl ,Harriet Rouse & By: William A. Strohl ,Harriet Rouse &
Bruce D. FisherBruce D. Fisher
22ndnd Edition, 2007 . Edition, 2007 .
Pages;15-17,242-243Pages;15-17,242-243. .
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Questions ?Questions ?