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POXVIRUSES

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.

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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Important properties
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 animal

reservoir.

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 synthesizer early mRNA, which is translated into early, nonstructural proteins, mainly enzymes required for subsequent steps in viral replication.
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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 by

immunofluorescence 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 critical factors 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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MOLLUSCUM CONTAGIOSUM VIRUS


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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MOLLUSCUM CONTAGIOSUM VIRUS


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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