Ds DNA Virus

7/27/2019 Ds DNA Virus

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Greek word herpein ("to creep"), referring to

the latent, recurring infections typical of this

group of viruses. Herpesviridae can

cause latent or lytic infections.


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Properties of herpesviruses

Enveloped double stranded DNA viruses.

Genome consisits of long and short fragments which may be orientated

in either direction, giving a total of 4 isomers.

Set up latent or persistent infection following primary infection

Reactivation are more likely to take place during periods of

immunosuppression

Both primary infection and reactivation are likely to be more serious in

immunocompromised patients.


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Structure

Herpes Simplex Virus (HSV) is a double

stranded (ds)DNA virus containing 130-230

Kbp DNA that belongs to Herpesviridae family

(Smiley et al. 2004). It contains three main

structural components. A central core holds

the viral DNA, an inner core is surrounded by

an envelope that is made of viral glycoproteinsand host cell membranes, and a capsid.


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Between the icosahedral capsid and the lipid

envelope is an amorphous protein layer called

the tegument. Overall, there are about 40 to

50 different proteins in the virion ("virion

structural proteins"). Some of these proteins

make up the icosahedral capsid, some make

up the tegument, and some are theglycoproteins in the envelope.


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Genome

HHV-6 has linear, double stranded DNA which containsan origin of replication, two 810 kb left and right directrepeat termini, and a unique segment that is 143-145kb

The HSV genome encodes for over 80 proteins (Khanna etal. 2004). There are three classes of viral genes that aretranscribed and translated in a specific order, including theimmediate early (IE; ), early (E; ), and late (L; ) genes.

( Immediate early genes (such as -TIF) are transcribed and translated first. Four(ICP0, ICP4, ICP22, and ICP27) of these five proteins from the IE genes serve asregulatory proteins that initiate transcription of early genes by the host cells RNApolymerase (Smiley et al. 2004). ICP4, however, is the main regulatory protein ofHSV (Jenkins and Turner 1996). Early genes serve to downregulate immediateearly gene expression and upregulate the third set of genes in infection, called lategenes. Late genes downregulate early gene expression and are structural proteins(Smiley et al. 2004).)


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After the late phase of infection, a viral capsidis formed in the nucleus that contains viral

DNA. The capsid buds through the nuclearmembrane and leaves the cell through theGolgi complex. During this process, the virusacquires its tegument and envelop, and the

host cell dies as virus is released. HSV is thenretrogradely transported along axons to thecell body of neurons to establish a latent

infection. This transport is accomplished bydynein and dynactin, which move HSV capsidsalong microtubules (Dohner et al. 2002).


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Epidemiology

HSV is spread by contact, as the virus is shed in saliva, tears, and

other secretions.

By far the most common form of infection results from a kiss given

to a child or adult from a person shedding the virus.

Primary infection is usually trivial or subclinical in most

individuals. It is a disease mainly of very young children ie. those

below 5 years.

There are 2 peaks of incidence, the first at 0 - 5 years and thesecond in the late teens.


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Epidemiology

Following primary infection, patients will experience recurrences.

The actual frequency of recurrences varies widely between

individuals.


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Pathogenesis

During the primary infection, HSV spreads locally and a short-lived

viraemia occurs, whereby the virus is disseminated in the body. Spread to

the to craniospinal ganglia occurs.

The virus then establishes latency in the craniospinal ganglia.

The exact mechanism of latency is not known, it may be true latency

where there is no viral replication or viral persistence where there is a low

level of viral replication.

Reactivation

-It is well known that many triggers can provoke a

recurrence. These include physical or psychological stress, infection;

especially pneumococcal and meningococcal, fever, irradiation; including

sunlight, and menstruation.


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Laboratory Diagnosis

Direct Detection

Electron microscopy of vesicle fluid

PCR - now used routinely for the diagnosis of herpes

Indirect or Serology Not that useful in the acute phase because it takes 1-2 weeks for before

antibodies appear after infection. Used to document to recent infection.


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Cytopathic Effect of HSV in cell

culture: Note the ballooning of

cells. (Linda Stannard, University

of Cape Town, S.A.)

Positive immunofluorescence test for

HSV antigen in epithelial cell.

(Virology Laboratory, New-Yale Haven

Hospital)


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Prevention

The virus is ubiquitous nothing can be done toprevent the transmission of infection inenvironmental terms.

Prophylactic chemotherapy may be given tothose suffering from frequent and severerecurrent herpes.

In clinical trials, a -interferon eye drops haveproved effective for the prevention ofrecurrent dendritic ulcers.


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Management

At present, there are only a few indications of antiviral chemotherapy, with the

high cost of antiviral drugs being a main consideration.

Acyclovirthis the drug of choice for most situations at present.

Famcicloviroral only, more expensive than acyclovir.


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HSV_vaccines

Several recombinant subunit vaccines are

being evaluated at present. There is evidence

to suggest that such vaccines may be effective

in reducing the frequency and severity of

recurrent disease in an already immune

individual, but their efficacy in preventing

primary infection is uncertain.


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The replication cycle of Herpes

Simplex virus

1. Specific proteins in the viral envelope attach tohost cell receptors on the cell membrane.

2. Penetration is achieved when the viral envelopefuses with the cell membrane releasing the

nucleocapsid directly into the cytoplasm. 3. The virion is uncoated and the viral DNA is

transported into the nucleus.

4. In the nucleus, the viral DNA is transcribed intoearly mRNAs which are transported to the cytoplasmfor the translation of early proteins. These earlyproteins are brought back into the nucleus andparticipate in the replication of the virus DNA intomany copies.


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The viral DNA is then transcribed into the latemRNAs which exit to the cytoplasm fortranslation into the late (nucleocapsid andenvelope) proteins.

5. The capsid proteins encapsidate the newlyreplicated genomes. The envelope proteins areimbedded in the nuclear membrane. 6. Thenucleocapsids are enveloped by budding

through the nuclear membrane, and the matureviruses are released from the cell throughcytoplasmic channels.


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Primary Infection: The Lytic Cycle

HSV infects its host through both lytic and latentinfection, and replication of HSV occurs within 15hours after infection (Jenkins and Turner 1996).

In the lytic cycle, HSV infects epithelial cellslocated in the mucosa, replicates, and causesepithelial cell death .

In order to infect epithelial cells, glycoproteins

(namely gB, gC, and gD) on the surface of HSVfuse with entry receptors on the host cellmembrane.


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There are three known types of entry

receptors located on the host cell that bind to

HSV during cell infection and fusion. Heparan

sulfate is a glycosaminoglycan (GAG), and it

binds to gB and gC (Spear et al. 2004).


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The sequence of events at the cell surface usually

involves the HSV-1 virion binding initially to heparan

sulphate, and then to the main receptor. The latter

can be one of several types of cell surface moleculeincluding some nectins, which are cell adhesion

molecules. The virion envelope then fuses with the

plasma membrane. Infection may also

occur by endocytosis, followed by fusion between the

virion envelope and the endosome membrane.


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Adenovirus


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Adenoviruses are medium-sized (90

100 nm), nonenveloped (without an outer lipid

bilayer)icosahedral viruses composed of

a nucleocapsid and a double-stranded

linear DNA genome.

The virus is composed of around 1 million

amino acid residues and weighs around

150 MDa


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Structure

Adenoviruses represent the largest

nonenveloped viruses. Because of their large

size, they are able to be transported through

the endosome (i.e., envelope fusion is notnecessary). The virion also has a unique

"spike" or fiber associated with each penton

base of the capsid that aids in attachment tothe host cell.


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Epidimiology

Adenoviruses are highly species specific. Fecal

oral transmission is common in children.


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Diagnosis

Adenovirus infections can be identified using

antigen detection, polymerase chain reaction

assay, virus isolation, and serology.


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Prevention

Good hygiene, including hand washing, is still thebest way to avoid picking up the adenovirus froman infected person.

In the past, US military recruits were vaccinatedagainst two serotypes of adenotypes, with acorresponding decrease in illnesses caused bythose serotypes. The vaccine is no longer

manufactured, and there are currently novaccines available to protect against theadenovirus.


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Treatment

There are no antiviral drugs to treat adenoviral

infections, so treatment is largely directed at

the symptoms.


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Genome

The adenovirus genome is linear, non-

segmented double-stranded (ds) DNA that is

between 26 and 45 Kbp. This allows the virus

to theoretically carry 22 to 40 genes.


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Entry of adenoviruses into the host cellinvolves two sets of interactions between thevirus and the host cell. Most of the action

occurs at the vertices. Entry into the host cellis initiated by the knob domain of the fiberprotein binding to the cell receptor. The twocurrently established receptors are: CD46 for

the group B human adenovirus serotypes andthe coxsackievirus adenovirus receptor(CAR) for all other serotypes.


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To enter the cells they use a receptor present in thehost cell called as CAR (coxsackie and adenovirusreceptor). The internalization of the virus particlesoccur through receptor mediated endocytosis. Afterentry the endosome containing the virus particlemigrates to nucleus and the genetic information of thevirus is released into the nucleus. Transcription of thefirst gene is done by the terminal protein attached withthe viral DNA. Viral mRNA is then transported to the

cytoplasm and translated into the viral proteins. Virusassembly takes place in the cytoplasm and the matureviral particles get released from the infected cells afterkilling them by accumulated adenoviral death proteins.


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Replicative Cycle

The adenovirus replicative cycle is divided intoearly and late phases with the late phaseoccurring when viral DNA replication begins.

Attachment-Penetration-Uncoating Adenovirus attachment is mediated by the

fiber which binds a specific receptor on thecell membrane. Subsequently the attachedvirus migrates to clathrin coated pits to form areceptosome and become internalized.


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Early Transcription

Viral gene expression is not a haphazard

process. On the contrary it is highly ordered

and carefully orchestrated in much the same

manner as genes are regulated for cell division

or embryonic development.


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SV40


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SV40 is an abbreviation for Simian vacuolating virus40 or Simian virus 40, a polyomavirus that is found inboth monkeys and humans.

Like other polyomaviruses, SV40 is a DNA virus that has

the potential toSV40 is an abbreviation for Simianvacuolating virus 40 or Simian virus 40,apolyomavirus that is found inboth monkeys and humans. Like other polyomaviruses,SV40 is a DNA virus that has the potential to

cause tumors, but most often persists as a latentinfection. cause tumors, but most often persists as alatent infection.
http://en.wikipedia.org/wiki/Polyomavirushttp://en.wikipedia.org/wiki/Polyomavirushttp://en.wikipedia.org/wiki/Monkeyhttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/Monkeyhttp://en.wikipedia.org/wiki/DNA_virushttp://en.wikipedia.org/wiki/DNA_virushttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/DNA_virushttp://en.wikipedia.org/wiki/Tumorhttp://en.wikipedia.org/wiki/Tumorhttp://en.wikipedia.org/wiki/DNA_virushttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/Monkeyhttp://en.wikipedia.org/wiki/Polyomavirus

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