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"The deviation of man from the state in which he was originally placed by nature seems to have proved to him a prolific source of diseases."

-Edward Jenner  

Virion Morphology 

 Poxvirus virions are enveloped virus particles with complex nucleocapsids, typically measuring 140-260 nm in diameter and 220-450 nm in length.  Under the electron micrograph, the virion appears brick-shaped or ovoid (in the case of orf & molluscum).  It is comprised of an external membrane that consists of a network of tubules, within which there lies a biconcave, dumbell-shaped core with two lateral bodies.  Given that many of the poxviruses are antigenically similar, infection with one poxvirus typically provides both specific and cross-protective immunity against other poxvirus infections.

 

 

 

 

 

 

Genomic Organization

The poxvirus genome, which encodes genetic information in the form of double-stranded DNA cross-linked at both termini, ranges in length from     186 kbp (variola) to 220 kbp (cowpox).  It is not surprising that the largest virions would encode a similarly large number of viral proteins.  Accordingly, the size of the poxvirus genome varies by individual virus but is as large or larger than herpesviruses, coding for more than 250 genes. 

In general, the nonsegmented, noninfectious genome is arranged such that centrally located genes are essential for virus replication (and are thus conserved), while genes near the two termini effect more peripheral functions such as host range and virulence.  One way poxviruses practice differential gene expression is by utilizing open reading frames (ORFs) arranged in sets that, as a general principle, do not overlap.  

Several viral families capitalize on repeated genomic sequences in their respective replication strategies.  Inverted terminal repeats, or ITRs, are found on both the 5' and 3' ends of the poxvirus genomes.  ITRs consist of a highly conserved section of approximately 100 bp, a set of ORFs, and an A/T-dense, incompletely paired hairpin loop that connects the two strands of DNA.

To enter the host cell, the virus binds to cell surface receptors and enters the cell via either endocytosis or direct fusion.  Following entry, the virions are released into the cytoplasm, where structure is translated into function as the virus prepares for replication. 

Viral Replication 

Poxviruses are unique among DNA viruses in that they replicate exclusively the cytoplasm (as opposed to the nucleus).  In order to do this, poxviruses carry with them the necessary enzymes for genome replication: viral transcriptase, transcription factors, capping and methylating enzymes, and a poly(A) polymerase.  In not relying on the host cell for these critical enzymes, poxviruses are able to initiate transcription of viral DNA shortly after entry.  

Viral replication then proceeds in two phases.  In the first, the poxvirus uses a virally encoded DNA-dependent RNA polymerase to make a finite number of immediate early mRNAs.  The mRNAs are then capped, methylated, and polyadenylated.  Another of the imediate early mRNA translation products is an uncoating enzyme, which functions by further uncoating the viral DNA and allowing the remainder of the early genes involved to be transcribed and expressed.  As an aggregate, early genes comprise approximately 50% of the genome.

 Genome replication is believed to involve self-priming, after which the products are cleaved to make virus genomes.  Late genes, which comprise the residual 50% of the genome, are expressed after genome replication, for late promoters depend on DNA replication for activity.