New antibodies and antigen of VZV

Varicella zoster virus (VZV, also known as human herpesvirus 3) is a ubiquitous alphaherpesvirus with a double-stranded DNA genome. VZV only naturally infects humans, with no animal reservoir; its main targets are T lymphocytes, epithelial cells and ganglia. VZV causes two human diseases, varicella (chickenpox) and herpes zoster (shingles). Varicella is a disease most commonly affecting children, teens, and young adults, while zoster is more common in adults and rarely seen in children.

The VZV virion consists of a nucleocapsid surrounding a core containing the linear, double-stranded DNA genome; a protein tegument separates the capsid from the lipid envelope, incorporating the major viral glycoproteins. VZV DNA consists of approximately 125 kbp with at least 69 open reading frames (ORFs). The linear sequence of VZV genes is similar to that of HSV-1, which is the prototype of the alphaherpesviruses, and complementation has been demonstrated for some genes. VZV is the smallest of the human herpesviruses and lacks genes for several proteins found in HSV, such as glycoprotein D (gD). VZV produces at least ten glycoproteins, five of the glycoproteins, gK, gB, gH, gL, and gE are essential for VZV replication. In contrast, the remaining five glycoproteins, ORFS/L, gN, gC, gM, and gI are dispensable. Still, their absence from the VZV genome affects replication in cell culture and pathogenesis assessed in differentiated human tissue.

The gE protein is produced most abundantly in VZV-infected cells; it is noncovalently linked to gI and has been shown to bind the Fc fragment of immunoglobulin G (IgG). The gB protein is the target of neutralizing antibodies and probably plays a role in virus entry. The amino acid sequence of gB is highly conserved between VZV and HSV-1, accounting for past observations of their antigenic relatedness. The gH protein appears to have fusion function, facilitating cell-to-cell spread of the virus; gH requires the presence of gL for glycosylation and transport to the cell surface. The gC protein is not essential for VZV replication; plaque-purified virus that does not express gC can be subcloned from VZV isolates, including the Oka vaccine strain.

Fig. 1 Linear diagrams of the 10 glycoproteins expressed by VZV
The clinical presentations of VZV are very characteristic, however diagnosis is important for determining the immune status before prognostic and therapeutic monitoring. Several methods exist including polymerase chain reaction (PCR), direct immunofluorescent assay (DFA), viral isolation and serologic assays that detect VZV-specific antibodies. Recent infection is suggested by the detection of serum VZV-specific IgM antibodies, but this can be less reliable for herpes zoster where specific antibodies are already present. The National VZV Laboratory at the CDC has developed a reliable IgM capture assay. Other current commercials assays for determining VZV immune status include ELISAs, latex agglutination, indirect-immunofluorescence assay (IFA) and enzyme-linked fluorescent immunoassay (ELFAs).

Creative Diagnostics now can provide a series of VZV gE monoclonal antibodies and a VZV gE antigen expressed in CHO that provide valuable tools for virology research.