Varicella-Zoster Virus Glycoproteins
Category: Virology
Varicella zoster virus has a smaller genome than herpes simplex virus and therefore encodes fewer glycoproteins. In a recent review nine VZV glycoproteins are profiled, including gE, gI, gC, gH, gL, gB, gK, gM, and gN. Although all VZV glycoproteins have HSV homologs, functions occasionally have greatly shifted. For example, VZV gE is the predominant VZV glycoprotein and exists as a monomer, dimer and trimer, as well as a gE/gI complex. VZV gE is essential, unlike HSV gE. Even though essential, mutations in gE had been detected in wild type VZV strains that exhibit an accelerated cell-spread phenotype. The VZV gC glycoprotein differs from HSV gC in that both transcription and translation of VZV gC are remarkably delayed in cultured cells; often VZV gC protein is difficult to detect altogether. The VZV gH/gL complex resembles the HSV gH/gL complex is that both are critical for virus induced fusion. Fusion is a prominent feature of VZV infected cells. Neutralization antibody to VZV gH dramatically reduces the spread of virus and limits pathogenesis in the skin. The VZV gB glycoprotein is also involved in virus-induced fusion. Of interest, four VZV glycoproteins (gE, gI, gH and gB) have functional endocytosis motifs in their cytoplasmic tail. Thus, all four are internalized from the cell surface in clathrin coated vesicles. This pathway appears critical for the process of virion envelopment in the assembly compartment. Even though abundant amounts of most glycoproteins are produced in cell culture, assembly of fully enveloped and infectious VZV particles rarely occurs. The particle:plaque forming unit ratio remains an extremely high 40,000:1. Likewise, the aberrant assembly process severely limits any assessment of egress mechanisms.
Further reading: Alphaherpesviruses: Molecular Virology
Further reading: Alphaherpesviruses: Molecular Virology
Varicella Zoster Virus Transcriptional Regulation
Category: Virology | Regulation
Varicella-zoster virus (VZV) encodes three immediate-early proteins, IE4, IE62, and IE63; however, only IE62 has TAATGARAT-like sequences in its promoter which are present in the promoters of each of the herpes simplex virus immediate-early proteins. The TAATGARAT-like elements on the IE62 promoter bind to VZV ORF10 protein, Oct, and HCF-1. In addition, histone methyltransferases are recruited to the IE62 promoter to modify chromatin to a transcriptionally active form. VZV IE62, the major VZV transactivator binds to VZV IE4 and IE63, and Med25, part of the mediator complex which upregulates gene expression. VZV IE62, IE4, and IE63 are present in the viral tegument where they may help to regulate transcription early in infection. IE63 binds to several cellular proteins including ASF1 and RNA polymerase II. Two hypotheses have been proposed for regulation of VZV gene expression during latency. First, relocalization of HCF-1 from the cytoplasm to the nucleus of sensory ganglia in response to stimuli associated with reactivation may help to augment transcription of IE62 to reactivate VZV from latency. Second, promoters of latent genes are maintained in a euchromatic state allowing their transcription, while promoters of genes not associated with latency are in a heterochromatic state resulting in repression of transcription.
Further reading: Alphaherpesviruses: Molecular Virology
Further reading: Alphaherpesviruses: Molecular Virology