Human Papillomavirus (HPV) Antibodies, Proteins & ELISA Kits

Human papillomavirus (HPV) is a viral infection that is passed on during skin-to-skin contact, particularly sexual contact. Papillomaviruses (PV), part of the family Papillomaviridae, are small DNA viruses that are not unique to humans. Depending on the host, papillomaviruses are capable of causing lytic, chronic, latent, and transforming infections.

There are over 200 varieties of HPV. More than 40 types of HPV are transmitted through sexual contact. Thus, HPV is the most common form of sexually transmitted infection (STI). HPVs infect mucosal and/or cutaneous skin, thus, causing common skin warts or lesions, usually on the hands or feet. In addition, HPV accounts for almost all cases of cervical cancer, as well as several other cancers, such as, penile, vaginal and oral squamous cell carcinomas (OSCC).

The different types of HPV are categorized into high risk or low risk groups depending on their oncogenic potential. Within the high risk category, types 16 and 18 are the most prevalent and carcinogenic. Together, they are responsible for ~70% of cervical cancer cases. HPV-related cancer is a significant global health burden. On an annual basis, HPV-associated cancers are causing nearly half a million deaths worldwide. In addition, recent studies indicate that HPV-positive OSCC incidence is increasing at an epidemic rate.

At present, there are three prophylactic HPV vaccines available; the bivalent HPV vaccine, the quadrivalent HPV vaccine and a nonavalent HPV vaccine. These vaccines are reported to be effective in protecting against 90% of HPV infection.

The HPV oncoprotein E2 plays a vital role in viral replication. E2 has several functions, namely, the enhancement of viral DNA replication and transcriptional activation/repression of viral promoters.

Oncoproteins E6 and E7 are the major viral factors involved in the initiation and progression of cervical cancer. These proteins induce genomic instability and overcome negative growth regulation.

SLC7A11 is a cystine transporter in head and neck squamous cell carcinoma (HNSCC). It has been demonstrated that when compared to HPV negative HNSCC, HPV positive tumours have reduced SLC7A11 expression. Thus, it has been proposed that SLC7A11 is a potential HPV-related biomarker in HNSCC.

Increased expression of proteins p16 and Ki67 is associated with the host viral response to acute cervical HPV infection. In cells with low copy and quiescent viral DNA, importin-beta, exportin-5, MCL1, and cFLIP expression is also increased. Thus, these proteins may serve as novel biomarkers of HPV.

Host defense mechanisms are generally successful in eliminating initial HPV infection for the majority of infected individuals.

Human alpha-defensin 5 is a potent antagonist of HPV infection. This cationic peptide inhibits furin cleavage of the HPV capsid protein L2 at the cell surface. Upon entry into the host cell, HPV DNA is recognized by cytosolic DNA sensors AIM2, IFN-Gamma, IFI16, and cGAS. In addition, IFI16 functions to detect foreign DNA in the nucleus. Viral DNA triggers the AIM2 inflammasome. This results in the maturation of IL-1B which is often activated in HPV16-infected lesions.

An association between clearance of HPV infection and increased expression of nucleic acid-sensing toll-like receptors (TLR2, TLR3, TLR7, TLR8, TLR9) has been found in women. Interestingly, IFN-Beta

HPV entry and functions in the clearance of latent HPV episomes in infected cells.

Plasmacytoid dendritic cells (pDCs) respond to HPV16 virus-like particles (VLPs) in cervical cancer tissue. Thereafter, following the activation of MYD88-dependent signaling, they secrete numerous cytokines, including IL-6, IL-8, IFN-Alpha and TNF-Alpha.

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HPV can modulate host gene expression and dysregulate protein function in order to evade host immune defense. As previously mentioned, the oncoprotein E7 is majorly involved in HPV-associated cancers. It interacts with DNMT1, stimulating methyltransferase activity. In an E7-dependent manner, CXCL14 expression is downregulated in HPV-associated cancer progression. HPV38 E7 recruits EZH2 to the promoter region of TLR9, thus repressing TLR9 transcription. Similarly, HPV16 E7 recruits HDAC1 and JARID2 to a regulatory region upstream of the TLR9 transcriptional start site, therefore, downregulating TLR9 expression. HPV E7 proteins recruit HDAC1 to promoters containing IRF1 response elements, thus inhibiting the transcriptional activity of IRF1. As a result, TAP1, IFN-Beta, and CCL2, are downregulated in HPV16 E7 expressing cells, as they are considered IRF1 responsive genes.

NF-kB is a key transcription factor in immune signaling. HPV deregulates NF-kB in order to repress proinflammatory cytokine production. High-risk HPVs enhance IFRD1 expression, thus decreasing K310 acetylation of NF-kB in keratinocytes. As a result, proinflammatory cytokines are downregulated. Similarly, E6 and E7 downregulate IL-8, IL-18, CCL2, and CCL20 expression. In addition, high-risk HPVs upregulate UCHL1 in keratinocytes. 

IDO1 is an immune checkpoint molecule that functions in the suppression of antitumor immunity. HPV16 E7 expression in mouse skin upregulates IDO1 expression in dermal dendritic cells.

TYK2 is vital for signal transduction. It binds to its receptor by various cytokines including IL-6 and IL-12. HPV18 E6 interacts with TYK2. This results in a reduction of IFN-alpha-induced phosphorylation in TYK2 and STAT2 proteins.

IRF3 plays a key role in the induction of immune responses against viral infections. It is selectively bound and inhibited by HPV16 E6.

Immunometabolism plays a key role in human health and disease. It describes the series of changes that occur within the intracellular metabolic pathways of immune cells during activation.

HPV is associated with ~ 5% of human cancers, primarily cervical cancer. One of the primary biochemical characteristics of cancer cells is the alteration of glucose metabolism. The majority of cancer cells increase glycolytic rates and glucose consumption. GLUTs are integral membrane proteins that function in the transportation of small carbon compounds such as monosaccharides. GLUT1 is expressed under the control of transcription factors including p53. This directly represses GLUT1 and GLUT4 transcription, thus, limiting glucose uptake in cancer cells. HPV E6-mediated degradation of p53 can lead to an overexpression of GLUT1 and subsequently, an increase in glucose uptake of cervical cancer cells. Through blocking minichromosome maintenance protein (MCM) loading onto chromatin, HPV1 E4 subsequently inhibits the initiation of cellular DNA replication. This is dependent on an arginine-rich motif which is located within the full-length form of the viral protein.

Assay Genie provides Glycolysis, Glucose Uptake, and Arginase immunometabolism assay kits that would support HPV research.

The best studied and most widely used animal models for HPV include the rabbit oral papillomavirus, cottontail rabbit papillomavirus, and mouse papillomavirus. It is important to note that animal papillomaviruses (PVs) have been vital throughout the development of HPV vaccines. Bovine, rabbit, and canine models have been implemented in the study of vaccination in the natural host. In addition, non-human primate PVs share similar evolutionary histories as their human counterparts and thus, act as a potential animal model for HPV research.

Assay Genie offers a wide range of animal model ELISA kits with the potential to support the advancing field of HPV research.