Molecular Pa Tho Genesis of Virus - FAHMI 2

8/7/2019 Molecular Pa Tho Genesis of Virus - FAHMI 2

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by:

Mohd Fahmi bin Mastuki (GS29777)

Master in Medical MicrobiologyFaculty of Medicine and Health Sciences

by:

Mohd Fahmi bin Mastuki (GS29777)

Master in Medical MicrobiologyFaculty of Medicine and Health Sciences

Molecular Pathogenesis of Virus Infections

MCB5702 Molecular VirologyLecturer: Prof. Tan Wen Siang

Assignment 1

MCB5702 Molecular VirologyLecturer: Prof. Tan Wen Siang

Assignment 1


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LEARNING OUTCOMES:

1. Explain the concept of pathogenesis in the context of

virus infections.2. Discuss the molecular basis for virus-induced

immunodeficiency and cell transformation by viruses.

3. Understand the ways in which virus infection may result

in cellular injury.

At the end of this session, you should be able to:

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INTRODUCTION

INTRODUCTION

viral replicative cycle

viral replicative cycle

Thefundamental

process of V IRAL

INFECTION

PRINCIPLES OFV IRAL DISEASES


The cellular response to

that infection may rangefrom : -

no apparent effect

cytopathology withaccompanying cell deathto hyperplasia or cancer.

Viral disease is s e har f l ab r ality t atres lts fr viral i fecti f t e st rga is .

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y Clinical disease in a host consistsof signs and symptoms.

y A syn rome is a specific groupof signs and symptoms.

y Viral infections that fail toproduce any symptoms in thehost are said to be inapparent(su clinical).

y In fact, most viral infections donot result in the production of disease. (Figure 1)

INTRODUCTION(cont )

INTRODUCTION(cont )PRINCIPLES OFV IRAL DISEASES


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http:// www.rabies-symptoms.org /


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Important principles that pertain to viral iseaseinclu e the following:

Important principles that pertain to viral iseaseinclu e the following:

1. Many viral infections are subclinical.2. The same disease may be produced by a variety of

viruses.3. The same virus may produce a variety of diseases4. The disease produced bears no relationship to viral

morphology.5. The outcome in any particular case is determined by

both viral and host factors and is influenced by thegenetics of each.

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V IRAL PATHOGENESIS

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is the process that occurswhen a virus infects a host.

is the process that occurswhen a virus infects a host.

A virus is pathogenic for a particular host if it can infect and cause

signs of disease in that host.

A virus is pathogenic for a particular host if it can infect and cause

signs of disease in that host.

+

A strain of a certain virus is more virulent than another strain if itcommonly produces more severe disease in a susceptible host.A strain of a certain virus is more virulent than another strain if itcommonly produces more severe disease in a susceptible host.


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Important features of two general categories of acute viraliseases (local, systemic) are compare in Ta le 30 1.

Important features of two general categories of acute viraliseases (local, systemic) are compare in Ta le 30 1.

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PATHOGENESIS OFV IRAL DISEASE

Understanding mechanisms of viral pathogenesis at the molecularlevel is necessary to esign effective an specific antiviral strategies.

Much of our knowledge of viral pathogenesis is based on animalmodels, because such systems can be readily manipulated andstudied.

viruses must enter a hostviruses must enter a host

To pro uce isease :-To pro uce isease :-

come in contact with susceptible cellscome in contact with susceptible cells

replicatereplicateproduce cell injuryproduce cell injury


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Steps in V iral Pathogenesis :-Steps in V iral Pathogenesis :-

Entry &PrimaryReplication

V iral Sprea& CellTropism

Cell Injury &Clinical Illness

Recovery fromInfection

V irus She ing


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A. Entry & Primary ReplicationA. Entry & Primary Replication

In order for host infection to occur, avirus must first attach to an entercells of one of the body surfaces

skinrespiratory tractgastrointestinal tracturogenital tractconjunctiva.

Most viruses - mucosa of the respiratory or

gastrointestinal tract

Most viruses - mucosa of the respiratory or

gastrointestinal tract

directly into the bloodstreamdirectly into the bloodstream

V iruses replicate at :the primary site of entry (usually)

the portal of entry


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B. V iral Sprea & Cell TropismB. V iral Sprea & Cell Tropism

Many viruses produce disease at sites distant from their point of entry.

(eg, enteroviruses = enter GIT CNS disease).

After primary replication at the site of entry, these viruses then spreadwithin the host (Figure 30 2).

mechanisms varybut the most common route is via the b loo stream or lymphatics.

The presence of virus in the blood is called viremia .


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Virions may be free in theplasma or associate withparticular cell types.

- Some viruses evenmultiply within those cells.

The viremic phase is short inmany viral infections.

In some instances, neuronalsprea is involve ; this isapparently how rabies virusreaches the brain to causedisease.

Virions may be free in theplasma or associate withparticular cell types.

- Some viruses evenmultiply within those cells.

The viremic phase is short inmany viral infections.

In some instances, neuronalsprea is involve ; this isapparently how rabies virusreaches the brain to causedisease.

V iral Sprea


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y

Viruses - exhibit organ and cell specificities.y Thus, tropism determines the pattern of systemic illness produced

during a viral infection .

Cell Tropism (response/reaction)

As an example, hepatitis B virus has a tropism for liver hepatocytes, andhepatitis is the primary disease caused by the virus.As an example, hepatitis B virus has a tropism for liver hepatocytes, andhepatitis is the primary disease caused by the virus.

Micrograph showing groun glass hepatocytes,which are seen in chronic hepatitis B infections

represent accumulations of viral antigen inthe endoplasmic reticulum.

Micrograph showing groun glass hepatocytes,which are seen in chronic hepatitis B infections

represent accumulations of viral antigen inthe endoplasmic reticulum.

http://uk.ask.com/wiki/Viral_hepatitis


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Tissue and cell tropism by a given virus usually reflect the presence of specificcell surface receptors for that virus.

The identity of the specific cellular receptor is known for some viruses but isunknown in many cases.

Tissue and cell tropism by a given virus usually reflect the presence of specificcell surface receptors for that virus.

The identity of the specific cellular receptor is known for some viruses but isunknown in many cases.

Cell Tropism (cont...)Cell Tropism (cont...)

http://me-you-and-virus.blogspot.com/2010/02/michelles-virus-replication-cycle.html


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V irus She ing


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C. Cell Injury & Clinical IllnessC. Cell Injury & Clinical Illness

Destruction of cells&

physiologic alterations(produced in the host by the

tissue injury)

Destruction of cells&

physiologic alterations(produced in the host by the

tissue injury)

evelopment of iseaseare partly responsible for the

Some tissues, such as intestinal epithelium, can rapidlyregenerate and withstand extensive damage betterthan others, such as the b rain.

Some tissues, such as intestinal epithelium, can rapidlyregenerate and withstand extensive damage betterthan others, such as the b rain.

intestinal epithelium neuron


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Many of the factors that determine degree of illness areunknown.

General symptoms associated with many viral infections, suchas malaise an anorexia , may result from host responsefunctions such as cytokine production.

Clinical illness is an insensitive indicator of viral infection ;inapparent infections by viruses are very common.

Some physiologic effects may result from non-lethalimpairment of specialized functions of cells such as loss

of hormone production to lethal impairment.

Some physiologic effects may result from non-lethalimpairment of specialized functions of cells such as loss

of hormone production to lethal impairment.


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V irus She ing


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D. Recovery from InfectionD. Recovery from Infection

The hosteither succum bs or recoversfrom viral infection.either succum bs or recoversfrom viral infection.

Recovery mechanisms include bothinnate and adaptive immune responses .Recovery mechanisms include bothinnate and adaptive immune responses .

Interferon (IFN) and other cytokines, humoral andcell-mediated immunity, and possibly other hostdefense factors are involved.

Interferon (IFN) and other cytokines, humoral andcell-mediated immunity, and possibly other hostdefense factors are involved.

Immune system


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St s i Vir l t g sis :-St s i Vir l t g sis :-

E try &rim ry

R lic ti

Vir l S r& C llTr ism

C ll I jury &Cli ic l Ill ss

R c v ry fr mI f cti

Virus S i g

Yeay..!


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E. V irus She ingE. V irus She ing

-- necessary step to maintain a viral infection in populations of hosts.

-- usually occurs from the body surfaces involved in viral entry.

In some viral infections, such as rabies, humans represent dead-end infections,and shedding does not occur.

-- necessary step to maintain a viral infection in populations of hosts.

-- usually occurs from the body surfaces involved in viral entry.

In some viral infections, such as rabies, humans represent dead-end infections,and shedding does not occur.

The last stage she ing of infectious virus into the environment.

http://www.healthcentral.com/genital-herpes/introduction-000052_1-145.html

This close-up view of earlyherpes outbreak showssmall, grouped blisters(vesicles) and lots of inflammation (erythema).

This close-up view of earlyherpes outbreak showssmall, grouped blisters(vesicles) and lots of inflammation (erythema).


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y It is usually accompanied by earlyproduction of infectious virions and

elimination of infection by the hostimmune system.

y Eg. influenza virus and rhinovirus.

Viral Persistence:Acute, Chronic & Latent Virus Infections

y An acute viral infection is characterized by :-y rapid onset of diseasey a relatively brief period of symptomsy resolution within days.

y An acute viral infection is characterized by :-y rapid onset of diseasey a relatively brief period of symptomsy resolution within days.

http://www.webmd.com/cold-and-flu/flu-guide/what-is-flu


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Chronic infections (also called persistent infections ) are those in whichreplicating virus can be continuously detected, often at low levels ; mild or noclinical symptoms may be evident.

Chronic infections (also called persistent infections ) are those in whichreplicating virus can be continuously detected, often at low levels ; mild or noclinical symptoms may be evident.

A latent infection is a situation in which a virus is present in the body, but itremains ormant , not causing any overt symptoms.

-- The host is still infected with the virus-- can pass the virus on to others

Latent infections can also be activated, causing symptoms and illness toemerge again.

A classic example of a latent infection is herpes simplex, which periodicallyflares up to cause cold sores before going dormant again.

A latent infection is a situation in which a virus is present in the body, but itremains ormant , not causing any overt symptoms.

-- The host is still infected with the virus-- can pass the virus on to others

Latent infections can also be activated, causing symptoms and illness toemerge again.

A classic example of a latent infection is herpes simplex, which periodicallyflares up to cause cold sores before going dormant again.

Caused byherpes simplex virus type 1

(HSV-1)


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Molecular Pa Tho Genesis of Virus - FAHMI 2

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