The Molecular Biology of Herpesviruses

 

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Herpesvirus Molecular Biology

Important Herpesvirus Facts

The Human Herpesviruses

New Findings

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Virion Morphology

The herpesvirus viral particle, or virion, is enveloped, with an icosahedral nucleocapsid that is approximately 100-300 nm in size.  The nucelocapsid, which surrounds the torus (a structure which contains the viral DNA genome), is 100 nm in diameter, and consists of 150 hexons and 12 pentons with a triangulation number of 16.  The virion nucleocapsid is then surrounded by a structure composed of virally-encoded proteins known as the tegument.  The tegument is the layer separating the nucleocapsid from the outer envelope, and varies in thickness at various points of the virion.  During viral infection of a new host cell, the tegument's role is to import already-synthesized viral proteins into the cell.  These proteins are then released, and are able to immediately perform a wide variety of functions, such as inhibiting host cell protein synthesis and cell-mediated immune responses, as well as facilitating viral protein synthesis.  Surrounding the tegument is the envelope, which contains approximately 12 virus-encoded glycoproteins. 

Genomic Organization 

Herpesvirus genetic information is encoded in double-stranded DNA that is approximately 120-230 kb in length.  In comparison to other viruses, the herpesvirus genome is large, and contains a wide variety of viral proteins.  One interesting observation about the herpesvirus genome is that, although the double-stranded genome is originally linear, it circularizes once reaching the nucleus of the infected host cell.     

The herpesvirus genome encodes a staggering amount of viral proteins, encoded in 70 genes in the smallest herpesviruses to 200 in the largest.  Both overlapping and antisense genes are encoded in the herpesvirus genome.  These genes are expressed temporally, with 3 distinct kinetic classes: immediate-early, early, and late.  The immediate-early genes generally encode regulatory proteins, which allow the expression of the early genes.  Once the early genes have been expressed, viral DNA replication as well as late gene expression can occur.  The diagram below of the herpes simplex virus I genome illustrates the complexity of the genomic organization of the herpesviridae family. 

Because of its phenomenal complexity, the herpesvirus genome is still in many areas not well understood.  Currently, research is being conducted to further explore the role of translational frame shifting, internal translation initiation sites, alternative slicing as well as other mechanisms in order to better understand the genomic organization of herpesviruses. 


Viral Replication

Herpesvirus replication is characterized by temporal gene expression, with the presence of 3 distinct kinetic classes: immediate-early, early and late genes.  The promoters for the specific genes in each kinetic class are generally expressed in the preceding class, thus regulating the temporal expression of certain viral genes.  The proteins encoded in the immediate-early genes are expressed first, and are generally involved in regulatory functions.  They are also instrumental in the activation of early gene translation, which leads to DNA replication.  The late genes, which are expressed last, encode structural proteins.  

Transcription of viral mRNA  is carried out by the host polymerase.  These mRNAs are then transported to the cytoplasm to be translated.  In general, each transcript encodes a single protein, and splicing is rare.  However, some mRNAs are spliced; nested and overlapping transcripts are also present in some herpes viruses.