3. Poxviruses

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POXVIRUSES

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POXVIRUSES

The family includes three viruses of medical

importance:

smallpox virus vaccinia virus

and molluscum contagiosum virus (MCV).

Poxviruses are the largest and most complex

viruses.

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SMALLPOXVIRUS

Disease

Smallpox virus, also called variola virus, is the agent of

smallpox,

It is the only disease that has been eradicated from the face of

the Earth.

Eradication is due to the vaccine. There is concern regarding the use of smallpox virus as agent of

bioterrorism

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Importantproperties

Poxviruses are brick-shaped particles containing

linear double-stranded DNA,

a disk-shaped core within a double membrane, and a lipoprotein envelope.

The Virion contains a DNA-dependent RNA polymerase.

This enzyme is required because the virus replicates in the

cytoplasm and does not have access to the cellular RNA

polymerase, which is located in the nucleus.

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Important properties

Smallpox virus has single, stable serotype, which is the

key to the success of the vaccine.

If the antigenicity varied as it does in influenza virus,

eradication would not have succeeded.

Smallpox virus infect only humans; there is no animalreservoir.

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Summary of Replicative Cycle

Vaccinia virus is nonpathogenic for humans,

is used for studies on poxvirus replication and as a vector

in certain gene therapy experiments.

After penetration of the cell and uncoating, the virion

DNA-dependent RNA polymerase synthesizerearly

mRNA, which is translated into early, nonstructural

proteins, mainly enzymes required for subsequent steps in

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Summary of Replicative Cycle

The viral DNA is replicated in typical semiconservative fashion,

after which late, structural proteins are synthesized that will

form the progeny virions. The virions are assembled and acquire their envelopes by

budding from the cell membrane as they are released from the

cell.

Note that all steps in replication occur in the cytoplasm, which

is unusual for a DNA virus.

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Transmission & Epidemiology

Before the disease was eradicated, smallpox virus was transmitted via

respiratory aerosol or by direct contact with virus either in the skin

lesions or on fomites such as bedding.

Prior to the 1960s, smallpox was widespread throughout large areas

of Africa;Asia and south America, and millions of people were

affected.

In 1967, the world Health Organization embarked on a vaccination

campaign that led to the eradication of smallpox.

The last naturally occurring case was in Somalia in 1977

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Pathogenesis & Immunity

Smallpox begins when the virus infects the upper

respiratory tract and local lymph nodes and than

enters the blood (primary viremia).

Internal organs are infected; then the virus reenters the

blood (secondary viremia) and spreads to the skin.

These events occur during the incubation period, when

the patient is still well.

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Pathogenesis & Immunity

The rash is the result of virus replication in the skin, but

there may be an immune component as well.

Immunity following smallpox disease is lifelong

Immunity following vaccination lasts about 10 years.

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Clinical findings

After an incubation period of 7-14 days, there is a sudden

onset of prodromal symptoms such as fever and malaise.

This is followed by the rash, which is worse on the face

and extremities than on the trunk(ie, it has a centrifugal

distribution).

The rash evolves through stages from macules to papules,

vesicles, pustules, and, finally, crusts in 2-3 weeks.

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Laboratory Diagnosis

In the past when the disease occurred, the

diagnosis was made :

either by growing the virus in cell culture or chick

embryos

or by detecting viral antigens in vesicular fluid byimmunofluorescence test

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Prevention

The disease was eradicated by global use of the vaccine,which contains live,attenuated vaccinia virus.

The success of the vaccine is dependent upon five criticalfactors

1) smallpox virus has a single, stable serotype(2) there is no animal reservoir, and humans are the only

hosts

(3) the antibody response is prompt: therefore, exposed

persons can be protected(4) the disease is easily recognized clinically; therefore,

exposed persons can be immunized promptly

(5) there is no carrier state or subclinical infection

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MOLLUSCUM CONTAGIOSUM VIRUS

Molluscum contagiosum virus (MCV) is a member of the poxvirus

family but is quite distinct from smallpox and vaccinia viruses.

It cause small, pink, papular, wartlike lesion of skin or mucosa

membranes.

The lesions have a characteristic cup-shaped crater with a white core.

Note that these lesions are different from warts, which are caused by

papillomavirus

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MOLLUSCUM CONTAGIOSUM

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MCV is transmitted by close personal contact, including

sexually.

The disease is quite common in children, and the lesions

can be widespread in patients with reduced cellular

immunity.

In immunocompetent patients, the lesions are self-limited

but may last for months.

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The diagnosis is typically made clinically

The virus is not isolated in the clinical laboratory, and antibody titers

are not helpful.

Removal of the lesions by curettage or with liquid nitrogen is often

effective.

There is no established antiviral therapy, but cidofovir may be useful

in the treatment of the extensive lesions that occur in

immunocompromised patients.

There is no vaccine.

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3. Poxviruses