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Papillomavirus E2 Research
Human Papillomaviruses are DNA viruses that cause skin lesions (keratinocytes). There are two categories of HPVs, high and low risk. High-risk papillomaviruses are HPVs-16, 18, 31, 33, 35, 39, 45, 51, 55, 58, and 59, which are often found on cancer cells. HPVs that produce skin lesions are low risk HPVs, but HPV-6 and HPV-11 are associated with genital warts. The mechanism of infection of these viruses has been widely research in particularly the oncogene protein E2/E1 and E6/E7, since they are consider the essential part for the development of cancer cells.

In a resent study, 99.7% of one thousand cases of invasive cervical cancer were HPV positive to HPV16, being the most common followed by HPV-18 DNA. High Risk HPV E6 and E7 are more active than E2 in cellular transformation than low risk HPVs. The oncogenes E7 and E6 have been found to change Keratinocytes by altering their cell cycle. E6 binds to P53 and degrades it preventing cell death (apoptosis) and promoting the replication of viral DNA. P53 is a repair mechanism that destroys any abnormal cells or arrests the cell cycle. Genetic changes in the DNA, such as, the introduction of viral DNA, which transforms and destabilizes the cell. Additional research has been performed in the apoptotic effects of papillomavirus E2. The research findings that the E2 protein in HeLa cells induce p53, causing arrest of the cell cycle and apoptosis. But, the induce p53 accumulation was not correlated to the cell growth arrest at G1 phase. This suggests that apoptosis and cell cycle arrest are independent of each other. Researchers used biochemical and genetic approaches to test the hypothesis that apoptosis by BPVI and HPV18 E2 proteins in HeLa cells is independent of p53. One experiment demonstrated that E2 induced apoptosis was set off by Bax, one of the best-known p53 promoting genes. Corroborating the independent pathway for cellular apoptosis and cell cycle arrest.

A comparative research study was conducted to study the transcription activity of high and low risk papillomaviruse E2 protein and affinity of the E2 binding regions of high and low risk HPVs. The study used protein encoded in HPV 16, HPV18, and HPV11 and Bovine -1, along with comparative DNA binding shift assays, cell free transcription systems, [|cofactors], to determine the affinity the oncoprotein E2 of both types of HPVs .The BPV1 has been used to model the replication of papillomaviruse. The viral gene of BPV1 gene contains several promoters that are activated by E2 protein .In vivo studies of DNA using HeLa cells revealed that different types of E2 proteins showed different transcription and repression activities based on the binding sites of E2. In vivo studies also revealed the high transcriptional activity of high risk HPV-16 E2, which suggests that HPV-16 has a very efficient E2 that regulates the E6/E7 oncoproteins that results in the control of the viral life cycle. The less efficient E6/E7 oncoproteins are expressed all lower levels in low risks HPVs. The regulation of the E6 promoter of the high risk E2 protein of the HPVs can lead to the development of cancer due to the viral integration.