Dr. Shatha S.Jumaah/Lecturer - Lecture Notes - TIU

Dr. Shatha S.Jumaah/Lecturer _____________________________________________ Genetics/Practical – 4th Stage /1st Semester

shatha.saadi@tiu.edu.iq https://tiu.edu.iq/

2020 - 2021

TIU - Faculty of Science Medical Analysis Department

1- List the general steps of pathogenesis and clinical course of viral infection.

2- Differentiate between local & systemic acute viral infection.

3- Describe the mechanisms of cell tropism, types of cell injury during viral

infection .

4-State the immunopathogenesis induced by viral infection.

5- Describe the mechanisms by which virus can escape from the host.

6- Explain the mechanisms of different types of persistent viral infections.

7- Differentiate between conventional and non-conventional viral infection.

Virus that can enter to the host, produced virus- host cell interaction, causing the sign and symptoms of a disease.

1. Implantation of virus at the portal of entry. 2. Local replication. 3. Spread to target organs (disease sites). 4. Spread to sites of shedding of virus into the environment.

1. Accessibility of virus to tissue. 2. Cell susceptibility to virus multiplication. 3. Virus susceptibility to host defenses.

Requirements to ensure successful infection in an

individual host

Sufficient virus must be available to

initiate infection

Cells at the site of infection

must be accessible,

susceptible, and permissive for

the virus

Local host anti-viral defense

systems must be absent or

initially ineffective.

1-Viral entry &Mode of transmission

2-Primary viral replication

3-Viral spread

4-Cellular injury

5-Cell &tissue tropisms

6-Host immune response

7-Viral clearance & establishment of persistent infection

8-Viral shedding

Through the following systems• -Respiratory Tract

• -Gastrointestinal Tract most common routes of viral entry

• -Skin

• -Urogenital Tract

• -Conjunctiva

• -blood born: by needles, insect vectors, blood Transfusion

person- to -person (infl.v.,herpes v.,HIV).

from mother to offspring ( rubella,HIV,CMV,Hepatitis B &C,parvo B19).

from animal to man ( rabies v.) – No transmission: due to reactivation of a latent, non-replicating virus can occurs within the individual infection (HSV1, HSV2 &CMV)

virus replicate at primary site locally as: influenza v. & rota v.)

these viruses spread locally over the epithelial surfaces, and there is no necessity for further systemic spread, no invasion to under lying tissues nor spread to distant site.

viruses that produce systemic manifestation distant from the site

of entry as: polio v.& Measles v.

The place of primary replication is where the virus replicates after

gaining initial entry into the host. This frequently determines whether the infection will be localized at the site of entry or spread to become a systemic infection.

Apart from direct cell-to-cell contact, the virus may spread via the blood

stream and the CNS.

takes place at susceptible organs/tissues following systemic spread.

Changes in the cell

appearance

Multinucleated Giant cells

Inclusion bodies

uncontrolled cell growth &prolonged survival (oncogenic v.)

due to inhibition of macromolecular synthesis either by inhibition of host cell protein synthesis or inhibition of DNA and RNA Synthesis.

leads to impairment of specialized functions of cells such as a loss of hormone production.

Incubation Period(IP)

Prodromal period

Specific illness period

Recovery period

1. Incubation Period( IP): usually asymptomatic, Necessary for clinical diagnosis, outbreak tracing, infection control, Can be:-

a. Short: less than a week (RESP, ARBOVIRUSES)

b. Medium: 1-3 weeks (MMR, polio, SARS)

c. Long: weeks-months (HEPATITIS, RABIES)

d. Very long: years (SSPE,PRIONS, PML )

2. Prodromal period: associated with non- specific symptoms

3. Specific illness period: characterized by sign & symptoms of the disease.

4. Recovery period: illness declines & patient regains good health.

cell killing e.g.

Diversion of the cell's energy

Shutoff of cell macromolecular synthesis

Competition of viral promoters & transcriptional enhancers for cellular transcriptional factors such as RNA polymerases, and inhibition of the interferon defense mechanism

Competition of viral mRNA for cellular ribosomes

Direct effect may result from

Indirect effect: (immunological attack)

1) Integration of the viral genome

2) Induction of mutations in the host genome

3) Inflammation

4) Host immune response.

In general, cellular immunity plays the major role in clearing virus infection whereas humoral immunity protects against reinfection.

Enhanced viral injury could be due to one or a mixture of the following mechanisms:-

Cytokines produced by

rota

Cytotoxic T-cell

Immune- mediated

pathogenesis

Complement

Infected enterocytes that stimulate the enteric neurons resulting in excess fluid and electrolytes secretion into the bowel lumen …..causing diarrhea .

Increased secondary response to cytotoxic T-cell are involved in the pathogenesis of hepatitis A,B &C (not causing CPE ),damage is due to recognition of viral Ag by

cytotoxic T-cell. Measles v. produce rash, cytotoxic T cell attacks infected vascular endothelial cell of skin.

1. Immune complex deposition in organs like skin, brain or kidney (rubella, measles) 2. (virus-antibody complement complex) deposited in various tissues e.g. (HBV, Parvo

B19; causing arthritis), and (RSV) causing pneumonia in infant due to maternal IgG-viral Ags complex.

Complement mediated cell lysis .

viral proteins block host immune mediators (IL1 /TNF)

2-Reduce the expression of class I MHC proteins (HIV/Cytomegalovirus)

3- Inhibit complement (HSV).

4-Virokines: some viruses synthesized RNAs that block phosphorylation

of initiation factor (elf-2), so that they reduce the ability of interferon to

block viral protein replication. (HIV/ Epstein Barr/ adeno v.)

5- Multiple antigenic types; viruses with multiple serotypes (rhino v.

more than 100 serotypes

Hepatitis C Virus: more than 6 serotypes.

The majority of viral infections are cleared but certain viruses may cause persistent infections. There are 2 types of chronic persistent infections.

Some time, the virus persists for long periods either intact or in the form of a subviral component (genome).

1- Integration of a DNA provirus into host cell DNA e.g.:- retroviruses

2- Immune tolerance: causing a reduced response to an antigen (no neutralization antibodies ), may be due to genetic factors, pre-natal infection, molecular mimicry

3-Virus –antibody complexes formation: which remain infectious

4- Location in an immunologically sheltered organ(restricted gene expression) e.g. brain .

5- Rapid antigenic variations

6- Spread from cell to cell without extra cellular phase.

7- Immunosupression direct infection of the cells of the immune system

itself e.g. Herpes viruses, Retroviruses (HIV) - often resulting in immunosuppression.

are those in which replicating virus can be continuously detected, often at low levels; mild or no clinical symptoms may be evident (the viral shedding continue for long period (as in chronic HBV or HCV or neonatal rubella &CMV).

the virus persists in an occult (hidden or cryptic) form most of the time when no new virus is produced. There will be intermittent flare-ups of clinical disease; infectious virus can be recovered during flare-ups. e.g.HSV; this virus enters a latent state in the cell of sensory ganglia once it's activated by a stress factors, recurrence of infection will occur.

Subacute seclerosing pan encephalitis (SSPE) which follows several years after

measles v. infection. **progressive multifocal leukoencephalopathy (PML), which

caused by JC-virus, a papova v., disease occurs primary in patient who have

lymphomas or immune compromised patients.

Non-Conventional viruses that causing (transmissible spongioform encephalpathies )

In human: Creutzfelds-Jacob disease /Kuru .

In animal: Mad -cow disease/ Scrapie -sheep

are Infectious particles that are composed solely of protein, no detectable nucleic acid E/M: revealed filaments. It's very resistant to U/V, heat, formaldehyde, nuclease but can be only inactivated by hypochlorite, sodium hydroxide and autoclave.

Differences between Prions & conventional viral infection

conventional prions Features

Yes No particle containing nucleic acid

v. gene Cellular gene particle containing protein Encoded by

Yes No inactivated by U/v or heat

icosohedral/helical filamentous(amyliod) E/M appearance

Yes No Ab production

Yes No Induce inflammation

Thanks for your

attention

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