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An Introduction to the Viruses

Topic 36 and Topic 37

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Size of viruses

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The Viral Structures and Shape

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Capsids

• All viruses have capsids- protein coats that enclose & protect their nucleic acid

• Each capsid is constructed from identical subunits called capsomers made of protein

• 2 types: – helical – iscosahedral

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Shape of Viruses, determined by the arrangement of proteins (capsomers) in the capsid

8Helical

9Icosahedral

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Icosahedral

• 20-sided with 12 corners• Vary in the number of

capsomers• Each capsomer may be

made of 1 or several proteins

• Some are enveloped

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Additional Structures in some Viruses, envelope and surface proteins

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Function of the envelope

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Complex Viruses-1• Two special groups of viruses termed Complex

viruses.• More intricate in structure than the helical,

icosahedral, naked or enveloped• These are :

– Poxviruses: very large viruses that contain a DNA core but lack a regular capsid, in its place are several layers of lipoprotein and coarse surface fibrils

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Complex Viruses-2• Bacteriophage : another complex virus

Polyhedral head

Helical tail

Fibers for attachment to host cell

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Naming viruses

• No taxa above Family (no kingdom, phylum, etc)

• 19 families of animal viruses• Family name ends in -viridae ,

Herpesviridae• Genus name ends in -virus, Simplexvirus• Herpes simplex virus I (HSV-I)

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• Family – Herpesviridae• Genus – Varicellovirus• Common name – chickenpox virus• Disease - chickenpox

EXAMPLE of VIRAL TAXONOMY

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Virus taxonomy based on viral characteristics

• In contrast to other discipline where taxonomy is well defined, viral taxonomy is much less structured and depends on a variety of characteristics including :

• Nucleic acid type : DNA or RNA• Nucleic acid strandedness: single stranded (ss) or

double stranded ( ds)• Presence or absence of an envelope• Capsid size or shape : icosahedral or helical• Host specificity, e.g. plant, animal, bacteria

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Example of the Taxonomic characteristics , used to describe a virus

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VIRAL REPLICATION

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Phage Replication

6 steps in phage replication

1. adsorption – binding of virus to specific molecule on host cell

2. penetration –genome enters host cell3. replication – viral components produced4. assembly - viral components assembled5. maturation – completion of viral formation6. release – viruses leave cell to infect other cells

22Fig 6.11

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Penetration

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Bacteriophage assembly line

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• Not all bacteriophages lyse cells• Temperate phages insert their viral DNA into the

host chromosome & viral replication stops at there until some later time.

• Lysogeny- bacterial chromosome carries phage DNA

Impact of Bacteriophages

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Animal Virus Replication

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Stages of Animal virus replication

1. adsorption2. penetration/ uncoating of genome3. duplication/synthesis4. assembly5. release

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Virus Adsorption

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Virus Adsorption• Once in the host, the virus must encounter ( recognize) a susceptible cell for the infection

cycle to proceed

• Susceptible host cells must :– Contain receptors for the virus– Be permissive or capable of supporting viral replication

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Virus Adsorption…..

• Host cell receptors must match the virus recognition sites for the virus to subsequently adsorb into the host cell

• Most virus receptors are surface glycoproteins

Host receptors

Virus receptors( glycoproteins)

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Adsorption

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Virus Penetration

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Virus penetration• Viral entry into host cells occurs through

one of the following methods:

– Endocytosis

– Direct fusion

– Nucleic acid translocation

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Endocytosis• All of the virus is engulfed and enclosed in a vacuole

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Direct Fusion• Host cell membrane fuses with the virus

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Nucleic acid translocation

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Nucleic acid translocationNon enveloped virus injecting its nucleic acid to the host cell

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Viral Uncoating

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Viral Uncoating

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Summary of Penetration/uncoating

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Duplication and Synthesis

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Duplication and Synthesis

DNA and RNA viruses replicate in different manner.

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DNA Replication

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The Most Common DNA Viruses• Adenoviruses• Cytomegalovirus• Epstein-Barr virus• Hepatitis B virus• Herpes simplex Types 1 &2• Papovavirus• Varicella-Zoster virus

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DNA Virus Replication-1

DNA dependent RNA polymerase is needed for the Transcription of mRNA from the DNA strand

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DNA Virus Replication….2

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DNA Virus Replication…3

The virus needs to code for proteins and enzymes that it can use in the Subsequent stages of its replicationAnd assembly ( e.g. DNA polymerase,Capsid proteins.

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DNA Virus Replication…4

DNA dependent DNA polymerase is Produce so that the DNA of the virusCan be replicated.

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DNA Virus Replication…5

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RNA Replication

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The RNA Viruses• Dengue viruses• Ebola virus• Picorna viruses• Hanta virus• Hepatitis A and C• HIV• Influenza virus• Mumps virus• Norwalk virus• Corona virus• Rotavirus• Rubeola Virus• RSV

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RNA Virus Replication

• RNA viruses enter the host cell already in an RNA form and the virus cycle occurs entirely in the cytoplasm.

• RNA viruses bring with them one of the following genetic messages:– a positive sense genome ( +RNA)– a negative sense genome ( -RNA)– a ds RNA– ss RNA which is converted to DNA ( latent retroviruses)

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RNA Virus Replication….1

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RNA Virus Replication…2

They have their own RNA dependent RNA Polymerase which it uses to transcribefrom The –RNA the + RNA strand which is use In the making the protein

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RNA Virus Replication…3

The + RNA strand is transcribe, theComplimentary copy is now a negative strand.

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RNA Virus Replication…4

It can’t

It can’t

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RNA Virus Replication (Retrovirus)

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RNA Virus Replication (Retrovirus)..

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RNA Virus Replication (Retrovirus)..

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Viral assembly

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Viral assembly…

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Viral Release

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Viral Release

Naked-nonenveloped and Complex viruses are released by cell lysis.

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Viral Release….

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Viral Release….

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Release by budding

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Viral Release….

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ReceptorsCell membrane

Host cytoplasms

RNA

spikes

SUMMARY OF VIRAL REPLICATION

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Host range• Spectrum of cells a virus can infect

– cell has to have a specific structure (receptor) on its surface for viral attachment

– cell has to contain all of the enzymes and materials needed to produce new virions

• May be one species or many– HIV (only humans) vs rabies (many animals)

• May be one tissue or many within a host– Hepatitis (liver) vs polio (intestinal & nerve cells)

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Differences between phage and animal virus replication

1. Animal virus replication is more complex than phage replication because host cells are more complex.

2. Animal viruses cannot inject their DNA.3. Lysogeny for phage, latency for animal

viruses

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VIRAL CPE

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Cytopathic effects- virus-induced damage to cells

1. changes in size & shape2. cytoplasmic inclusion bodies3. nuclear inclusion bodies4. cells fuse to form multinucleated cells5. cell lysis6. alter DNA7. transform cells into cancerous cells

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Cytopathic changes in cells

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Inclusion body

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Alteration of host membrane by insertion of viral proteins that trigger CMIR responses against the host cell

Cytotoxic T cell will kill virus infected cells

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Transformation or conversion of cell division to cells that divide indefinitely ( tumors ,warts)

Induces hyperplasia of the host cells

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Host Response to Viral Infections

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• Host Cell response includes :

– Antibody response

– Cellular Immune response

– Interferon production

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Antibody Response

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Cellular Immune response

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Interferons

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Diagnostic Virology

How do we grow viruses?

Obligate intracellular parasites require appropriate cells to replicate.

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Growing animal viruses

1. live animals 2. bird embryos – chicken, duck; intact, self-

supporting unit, sterile, self-nourished3. cell culture- cell lines

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Virus laboratory

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Cell Culture

• Cell culture is the process by which prokaryotic, eukaryotic or plant cell are grown under controlled conditions.

• "cell culture" now , refers to the culturing of cells derived from multicellular eukaryotes, especially animal cells.

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Cell lines• Cells that are cultured directly from a subject are known as

primary cells. – primary cell cultures have limited lifespan– after a certain number of population doublings cells undergo the

process of senescence and stop dividing, while generally retaining viability.

• An established or immortalised cell line has acquired – the ability to proliferate indefinitely either through random

mutation or deliberate modification, such as artificial expression of the telomerase gene

– There are numerous well established cell lines representative of particular cell types.

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Established human cell lines

• One of the earliest human cell lines, descended from Henrietta Lacks, who died of cervical cancer .

• The cultured HeLa cells shown below have been stained with Hoechst turning their nuclei blue.

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Tissue Culture

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Tissue Culture

91No virus virus

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Egg Inoculation

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Egg inoculation …

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Diagnosis of viral diseases

• More difficult than other agents• Consider overall clinical picture• Take appropriate sample

– Infect cell culture- look for characteristic cytopathic effects

– Screen for parts of the virus– Screen for immune response to virus

(antibodies)

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diagnosis

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Thank you end of lecture !