Pathology Of Hpv And Hpv Antiviral Development

2581 Words11 Pages
E5 Inhibition for HPV Antiviral Development

MEDS 523 Final Paper
Alice Chang

Background
Epidemiology of HPV
Human Papillomavirus (HPV) is a DNA virus that infects the keratinocytes of human skin and mucous membrane. It is the most common sexually transmitted infection in the world. An estimate of 79 million people in the United States are currently infected with HPV(1). With over 100 types of the virus, at least 40 types can infect the genitalia, mouth and throat. Particularly, HPV-16 and HPV-18 cause approximately 70% of cervical cancers. Transmission occurs through sexual intercourse, but can also occur through non-penetrative sexual activities.
Gardasil was the first HPV vaccine developed in 2006, followed by
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The proteins are E1-E7 and L1-L2. E stands for early, while L stands for late. E6 and E7 are the two most studied proteins. They have important roles as p53 tumor suppressor and inhibitor of differentiation, respectively(3). Although both E6 and E7 have garnered much attention as potential therapeutic targets, E5 is largely unrecognized.

E5 is a protein that alters the activity of cell cycle regulators. The phenotype of the cell changes when E5 is expressed. E5 acts at the early stage during carcinogenic progression; research has revealed that E5 is extinguished by integration of the viral genome during the progression to cervical cancer. E5 contributes to cancer development significantly through its mechanism of immune avoidance. As illustrated on figure 1, research suggests that it does so by interacting with B cell receptor-associated protein 31(BAP31). This interaction, labeled #1, induces loss of the surface MHC I expression in infected cells and prevents presentation of viral antigen to effector T-cells. Another mechanism can be observed on figure 1, marked #2. E5 also enhances the actions of E6 and E7 by modulating the transit of signaling proteins through the endoplasmic reticulum. Specifically, E5 interacts with the vacuolar H-ATPase. This interaction promotes recycling of the receptors on cell surface, resulting in constant signaling of epidermal growth factor receptor (EGFR). Increased EGFR signaling leads to activation of MAPK pathway. The MAPK pathway, in
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