Chickenpox and Shingles Antibodies, Proteins & ELISA Kits

Chickenpox (varicella) and shingles (herpes zoster) are illnesses caused by the varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3). VZV belongs to the subfamily Alphaherpesvirinae and it is found in every location around the world.

VZV is transmitted through aerosols when infected people cough and sneeze or else it can be passed between people if there is direct contact with skin lesions. VZV is particularly contagious in temperate climates in comparison to tropical locations. Chickenpox occurs when VZV infects non-vaccinated hosts and it can remain dormant in the body. Shingles is when there is reactivation of latent VZV infections. Both illnesses can occur at any stage of life but chickenpox is most commonly found in children under 10 years of age and shingles is predominantly found in individuals over 50 years of age.

Symptoms can include aches and pains, nausea, malaise, photophobia, headaches, fever, rashes, blisters, scabs and oral sores. In severe cases, VZV infections can lead to encephalitis, pneumonia and vasculopathy. There are currently different vaccines for VZV to prevent the development of these aforementioned symptoms and they prevent roughly 70-90% of infections. Varivax® and ProQuad® vaccines are used to prevent people contracting chickenpox and Zostavax® and Shingrix® vaccines are used to prevent people acquiring shingles. While there has been a massive reduction in both chickenpox and shingles over recent years, there is still a need for more research to improve vaccine development.

Understanding the function of VZV antigens can aid in chickenpox and shingles vaccine development. The VZV genome encodes open reading frames (ORF0-ORF71) which have numerous different roles whereby some ORFs aid in viral attachment and host cell entry. VZV also encodes 7 glycoproteins, gB, gC, gE, gH, gI, gK and gL.

Assay Genie provides recombinant proteins for ORF9 and ORF26 VZV antigens. As well as this, Assay Genie provides an envelope glycoprotein (gE) recombinant protein which is required for VZV infectivity. gE binds to the insulin-degrading enzyme (IDE) cellular receptor and it has been shown through numerous studies that IDE is required for VZV infections and the spreading of VZV between cells.

Understanding what host receptors bind to VZV antigens and cause the induction of signaling pathways can aid in chickenpox and shingles vaccine development. It has been shown that when monocytes are exposed to VZV, toll-like receptor 2 (TLR2) gets induced and nuclear factor kappa light chain enhancer of activated B cells (NF-kB) dependent secretion of interleukin-6 (IL-6) occurs. TLR9 can recognize viral double-stranded deoxyribonucleic acid (dsDNA) of VZV. As well as this, infection with VZV activates the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome when the nucleotide-binding and oligomerization domain (NOD)-like receptor NLRP3 recognizes pathogen-associated molecular patterns (PAMPs) of VZV.

VZV has adapted many mechanisms for evading the host immune system during infections. Interferon (IFN) is a key component of the immune response and it has been shown that IFN-alpha is particularly important for controlling VZV infection, whereby it can reduce the severity of the disease. Studies have shown that VZV can affect IFN signaling through it’s interactions with signal transducer and activator of transcription 1 (STAT1) whereby it not only impairs STAT1 activation but VZV also impairs IFN-alpha production.

When VZV is detected by immune cell receptors, there is the activation of transcription factors such as NF-kB and interferon regulatory factor 3 (IRF3) which causes the expression of IFN-beta to occur. However, VZV is capable of down regulating NF-kB and it does not activate TANK-binding kinase 1 (TBK-1) which is needed for coordinating the activation of IRF3. It has been shown that both IE62 and ORF47 encoded VZV proteins are able to alter the phosphorylation of IRF3, blocking the production of IFN-beta.

As well as this, VZV evades detection by T cells by downregulating major histocompatibility complex class I (MHC class I) by impairing MHC class I transport from the Golgi compartment to the cell surface. VZV is also able to inhibit IFN-gamma induced MHC class II expression.

It is important to get a better understanding of the host immune response to VZV in order to develop more efficacious vaccines against the virus. Even though there is a robust immune response generated during chickenpox infections, VZV is not completely eliminated from the body because it can gain access to neurons in the sensory ganglia where it resides during a latent infection and can later be reactivated causing shingles.

Some commonly observed cytokines which are produced during both chickenpox and shingles are IL-6, IL-8, IL-10, IL-1beta and tumor necrosis factor-alpha (TNF-alpha). As well as this, natural killer (NK) cells secrete both IFN-gamma and granulysin during VZV infections.

More recent studies have shown that there are also elevated levels of IL-4, IL-12, IL-17, IL-21 and IL-23 in shingles infections in comparison to control patients who are not infected with VZV.

Immunometabolism is an important area of science which encompasses regions of metabolism and immunology. Many of the functional capacities of immune cells are dependent on the metabolic state of the cell and its capability to mount an immune response.

At present there is very little research covering how immune cell metabolism is affected by VZV infection and this could be a possible research area to investigate in the future. Assay Genie provides a wide range of immunometabolism assays such as glycolysis and fatty acid oxidation assays kits.

Animal models are useful research tools which are often used in early stages of therapeutic product development and pathogenesis studies. There have been numerous studies which have investigated VZV pathogenesis in severe-combined immunodeficient (SCID)-humanized (SCID-hu) mouse models. The SCID-hu model has been used to analyze VZV genes during infection and the function of ORF proteins for the spreading and infectivity of VZV in susceptible hosts. As well as this, rat models such as Wistar rats have been used in VZV research to analyze aspects such as unique features of VZV-induced pain. Non-human primates have also been used extensively in VZV research whereby the rhesus macaque model is capable of developing a disease which has a close resemblance to chickenpox and the kinetics of the immune response developed is similar to VZV in children. As well as this, guinea pigs have been used in studies to improve VZV research.