An Overview of VZV

What is VZV?

Varicella zoster virus (VZV, also known as human herpesvirus 3) belongs to the genus Varicellovirus in the subfamily α-herpesviruses of the Herpesviridae family. VZV is an enveloped double-stranded DNA virus of low environmental resistance and 150-200 nm in size. The genome is 125 kb in length and encodes at least 71 unique open reading frames and associated promoter sequences. The icosahedral capsid has 162 capsomers and is surrounded by a lipid envelope comprising of host cell components and virus encoded glycoproteins. Five VZV branches have been identified, with the most divergent branch still having 99.8% sequence conservation.

The genome consists of a unique long region (UL) of ~105,000 bp, a unique short region (US) of ~5,232 bp, and internal repeat (IR) and terminal repeat (TR) regions. About 2/3 of the open reading frame (ORF) is required for in vitro replication, most of which are conserved genes in herpesviruses, including eight glycoproteins, proteins involved in DNA replication, and proteins involved in functions such as DNA cleavage and packaging, nucleic acid metabolism, and capsid assembly, such as the large and small subunits of the viral ribonucleotide reductase (ORF18 and ORF19), the two subunits of the viral DNA polymerase (ORF16 and ORF28), and the single-stranded DNA binding protein (ORF29), among others.

Figure 1. VZV genome and virion structure
(Source: Zerboni L, et al. 2014)

The primary targets of VZV are T lymphocytes, epithelial cells, and ganglia. Varicella is caused during primary infection, during which time VZV lurks in ganglion neurons. As cellular immunity to VZV wanes with age or impaired immune function, VZV reactivates, leading to herpes zoster. Herpes zoster can be complicated by chronic pain (postherpetic neuralgia (PHN)) and other serious neurologic and ocular disorders (e.g., meningoencephalitis, myelitis, cerebral nerve palsy, vasculopathy, keratitis, and retinopathy), as well as by a variety of internal and gastrointestinal disorders, including ulcers, hepatitis, and pancreatitis.

VZV Test

• Detection of virus

Acute VZV infection is diagnosed by detection of the virus. One of the preferred methods is the polymerase chain reaction (PCR) to detect the viral genome in cystic fluid, cerebrospinal fluid, tissue, bronchoalveolar lavage, EDTA blood, or amniotic fluid. A more specific point is its ability to test cerebrospinal fluid in cases of suspected acute central nervous system infections, as well as amniotic fluid in prenatal diagnosis following chickenpox during pregnancy. In immunosuppressed patients with herpes zoster, detection of VZV DNA in the blood may be useful to verify the potential risk of spreading the infection. Isolation and culture of VZV is time-consuming, requires extensive experience, does not have clinically relevant sensitivity, and is only suitable for blister fluids containing high viral loads. Immunofluorescent assays using monoclonal fluorescein-labeled antibodies can correctly identify viral isolates, and commercially available kits are available for direct qualitative detection, but have low sensitivity and specificity.

Table 1. Methods for the detection of VZV

(Source: Sauerbrei A 2016)

• Detection of antibodies

Serologic VZV diagnosis is indicated when there is a need to determine the status of susceptible populations to initiate active or passive immunoprophylaxis. There is no need to determine antibody status after varicella vaccination in healthy children, adolescents, and adults, as opposed to immunization status modification, which is more recommended for immunodeficiency vaccinees and healthcare workers.

In the laboratory, the specific antibody to VZV was detected by ligand test or partial immunofluorescence test. No matter which test method is used, each result interpreted by the respective laboratory as positive for anti-VZV antibodies can be used as a criterion for immunity against chickenpox. Commercial test kits have different sensitivities, so very low antibody titers cannot be recognized. Therefore, high sensitive detection methods, such as special glycoprotein enzyme-linked immunosorbent assay (ELISA) or membrane antigen fluorescent antibody (FAMA) test, should be used to control the immune status and carry out vaccine research after varicella vaccination. In addition, the reason for the low sensitivity of many commercially available VZV immunoassays may also be related to the occurrence of cross-reactivity with other herpesviruses.

Table 2. Methods for the determination of VZV-specific antibodies

(source: Sauerbrei A. 2016)

Consequently, inhibiting NRF2 activity holds promise as a therapeutic strategy for patients with NRF2-addicted cancers, as it can disrupt the cancer cells' reliance on NRF2-mediated cytoprotection. On the other hand, it is worth noting that NRF2 activation in immune cells within the host can significantly suppress cancer cell growth. This suggests that NRF2 inducers might also have therapeutic potential for treating certain cancers.

VZV ELISA Kits

VZV Antibodies

VZV Antigens