mlt503_l4 - virus host interaction

8/8/2019 MLT503_L4 - Virus Host Interaction

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MLT503 LECTURE 3

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By:Mohd Fahmi Mastuki

PM Dr Zuridah Hj HassanDepartment of Medical Laboratory Technology

Faculty of Health Sciences, UiTM


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1. Levels of virus transmission2. Sites of virus transmission3. Pathogenesis

- Determinants of pathogenicity- Sequence of events in viral infections- Forms of viral-host interactions- Outcomes of infection (pathology)

4. Effects of viruses on cells- Cell death- Transformation- Latent infection- Persistent infection

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Learning OutcomesAt the end of the session, you should be able to describe:


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Horizontal Vertical Zoonotic

1. Levels of virus transmission


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Transmission of disease fromperson to person

Common routes:

a) Respiratory route e.g.through sneezing, closecontact, aerosols (i.e.Influenza, measles)

b) Faecal-oral route e.g.Enterovirus naked virus

and not affected by bile,protein capsid resistant tostomach acidity andintestinal proteases.

Horizontal virus transmission


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c) Venereal route inflammationof the mucosa due to traumamay facilitate transmission of AIDS, herpes, genital wartsduring intercourse.

d) Cutaneous route mechanicalabrasions and animal/insectbites can facilitate virustransmission.

e) Inoculation transmittedthrough blood donation orsharing of needles amongintravenous drug abuser.

Horizontal virus transmission (cont..)


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Transmission of disease from motherto infant :a) Transplacental cause congenital infection

(e.g. CMV, HIV, rubella)b) Perinatal occurs as fetus passes through

the infected birth canal.

c) Breast feeding e.g. HIV

Vertical virus transmission


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Occurs in animals but sporadicallytransmitted to human . Man is usually theterminal host.

a) Rabies virus through bite of infected dog orcontact with infected animal excreta or secretions.

b) Via vector arthropods (mosquitoes) which pick upthe virus when feeding on an infected animal hostand transmit to human.

c) Contact with urine/droppings of infected rodents e.g. Hantavirus

Zoonotic transmission


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Hantaviruses


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2.0 Sites for viral entry / exit

1. SkinVia abrasions epidermis, usuallylocal since no nervesor vessels e.g. HPVthat cause warts)

Via bitesVia conjunctiva

2. RT3. GIT4. Urogenital


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Genital human papillomavirus (HPV) is found to be one of the most commonly affected sexually transmitted

infection (STI).

The virus infects both the skin and the mucous membranes.

warts


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m


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Children with the respiratory syncytial virus (RSV ), which causes a range of illnessesfrom mild colds to the more serious viral pneumonia.


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- Determinants of pathogenicity

- Sequence of events in viral infections- Forms of viral-host interactions- Outcomes of infection (pathology)

3.0 Pathogenesis

The origination and development of a disease


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Virus factors:i. Cell tropism Some have a wide range,others may have special receptors e.g.

rabies virus affinity for Ach receptorsin the nervous tissue.ii. Mutation may increase virus

virulence e.g. influenza virus dependon primary structure of virushemaglutinin.

- Determinants of pathogenicity


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Host factors (that influence the

outcome of viral infection)i. Age more serious in children e.g. EBV, RSV,coxsackie.

ii. Nutrition more serious if malnourishedassociated with depressed cell-mediatedimmunity (CMI)

iii. Genetic factors HLAB35 +ve individualsseem to be at higher risk for developing AIDS,HLADR5 is associated with greater risk of developing Kaposis sarcoma.


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Entry most common respiratory tract or skin.In some cases, remain localize to the site of entry. Most cases, the infection at the portal of entry is asymptomatic or only mild and

eventually virus spreads to secondary tissues. Spread : -

- Contagious (limited to portal entry)

- Systemic spread Target organs e.g. Coxsackie B (heart causing

myocarditis), Coronavirus (common cold)

- Sequence of events in viral infections


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Limited to portal of entry most URTI,warts.

Short incubation period (2-3/365) Viremia occur but only after the diseasehas already been clinically manifested.

Reinfection common secretory IgA offersome protection against reinfection of mucosa.

Contagious spread


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After gaining access to the body, the virusenters the blood stream, viremia ensues, virusspread to other tissues before the disease isclinically detectable.

IP longer 2-3 weeks Activation of the RES leads to the elimination of

virus (abortive infection) and viral multiplicationin RES leads to second viremia.

Reinfection systemic antibodies play asignificant role in protection against reinfection.

Systemic spread


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1. Productive infection only possible if the infected cells are permissive (i.e.they allow the viral particle to replicate

and produce infectious progeny).

2. Abortive infection occurs when a virusgains access to a cell, but the cell diesbefore the virus complete its replicativecycle.

Types of Viral Infection


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3. Persistent infection results from a stablerelationship between cell growth and viralmultiplication. Do not disturb essential cellfunctions significantly enough to cause celldeath. The following viruses caused this typeof infection:

- viruses released by budding (since cell type isnot required for viral release)

- Viruses that infect cells do not express MHCwhich are involved in the presentation of viral-derived peptides to the immune system.

Ab production towards


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Ab production towardsviral infection e.g. HIV


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- Lytic viruses that are prevented fromdisseminating by antiviral antibody of IFN

- Viruses of reduced virulence which grow betterat 31 33 C than at 37 C (those strainsisolated from infected cell cultures)

- Defective interfering (DI) particles, which lack aportion of the genome, do not multiple bythemselves, but interfere with themultiplication of infective viruses.


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Sporadic release of progeny virus. Virus multiplication begins but is

arrested at a later stage. Associated with DNA viruses (herpes). Latent infection can be reactivated

causing cyclic disease that is notprogressive.

Latent infection


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Special assays are required to reveal thepresence of a virus causing an inapparentinfection

- e.g. BK virus infects most individual byadolescence and sets up inapparent infectious

foci in the kidneys and proliferates whenimmunocompromised.


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The effects of viral infection on infected hostcells varies.

Infection may be inapparent , inducecytopathology (which often results in celldeath, or induce cellular transformation (whichis associated with immortalization of theinfected cell).

Outcomes of Virus Infection(Pathology)


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Associated with the presence of live viralparticles in the material studied.i. Morphologic changes cell rounding

ii. Nuclear changes pyknosis (changes innuclear structure, margination of chromatin)

iii. Cell membrane changes more permeable,cells tend to agglutinate with gp bindinglectins such as concanavalin A.

Cytopathic effects (CPE)


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- Cells tend to fuse with uninfected cells viafusion proteins leading to formation of giantmultinucleated cells, syncytia (large masses of cytoplasm containing hundreds or thousands of nuclei.

Giant multinucleated cells


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iv. Inclusion bodies- tend to be located in nucleus of infected cells,

cytoplasm (Negri bodies in rabies infectedindividual).

v. Necrotic and degradative changes seen inlate stages of viral infection, preceding cell lysis.


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The functional alterations that result in celldeath can be grouped as follows:

i. Inhibition of host macromolecular biosynthesis

ii. Abnormal membrane permeabilityiii. Inhibition of host DNA and RNA synthesis

C f ll d h i i l


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Causes of cell death in viralinfected cells

The reactions to viral infection seen ininfected tissues result from a

combination of cell damage andinflammatory changes.

The inflammatory cells in viral infectionsare lymphocytes and monocytes .


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i. Lungs. Interstitial pneumonia, characterized bymononuclear cell infiltrates in the alveolarwall.


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ii. Hepatic tissue. Cell necrosis and fattyinfiltration.


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iii. Renal tissue . Desquamated cells with typicalinclusion bodies can be detected in the urine of patients with rubella, mumps, measles.

iv. CNS - viral encaphilitis can be primary orsecondary

- viral meningitis (enteroviruses)

Characters of cells transformed by viruses


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Changes in the morphological, biochemical or growth parameters of acell.

Characteristics of transformed cells caused by viruses:- possesses viral genome (all @ part)- Morphologic changes (transformed cells in culture grow in random

orientation and are rounded in shape)- loss of anchorage dependence- loss of contact inhibition (overlap not monolayer, so in cell culture

foci seen)- Colony formation in semi-solid media- Decreased requirements for growth factors- Cells is not killed but change to a cancerous cell(failure of the normal regulatory mechanisms controlling cell growth and lifespan. As a result, tumor cells continue to divide and grow under circumstances in which normal cells do not).

Characters of cells transformed by viruses

Characters of cells transformed by viruses (cont )


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Changes in membrane transport properties sugars

and nutrients transported at higher rate. Expression of tumor-associated surface antigen. Changes in composition of the plasma membrane.

- reduced density and size of cellular glycolipids(important in contact inhibition)

- reduced fibronectin content, thus increase fluidity of membrane and contribute to morphologic changes

associated changes with malignant transformation. Mediators

- proteins encoded by oncogenes

Characters of cells transformed by viruses (cont..)


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Identifying viral oncogenic behavior


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Less strict criteria:

- visualization of viral structures (antigen or genome)on tumor cells.

- establishment of an epidemiologic link between a

given malignancy and a given virus.- isolation of a suspect virus from tumor tissue and

determination of the ability of the suspect virus totransform cells in vitro.

Identifying viral oncogenic behavior Best evidence : isolated virus causes a tumor in an

experimental animal, and reisolation or cloning of the same virus causes a second tumor in anotheranimal.

Oncogenes


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A transforming genes which encodes a protein capable

of inducing cellular transformation.

Oncogenes

Have a homologous


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Have a homologouscounterpart (proto-oncogenes) in normalcells.

- viral oncogenes (v-onc )in retroviruses.

- v-src gene encoded byRous Sarcoma virus (inbaby hamsters); itshomologous cellularproto-oncogene isdesignated as c-src .

- not essential for virusreplication.

- needed fortransformation and

tumor promotion.


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mlt503_l4 - virus host interaction

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