E5 Inhibition for HPV Antiviral Development
MEDS 523 Final Paper
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 …show more content…
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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Its locus is particularly amplified in these noted tumours leading to the progression of these cancers, it can be suppressed by p53 (tumour/ proliferation suppressor) which represses the EZH2 promoter, resulting inhibition of cell proliferation and invasion (Bracken, 2003; Xiao, 2011).
Human Papillomavirus(HPV) is the most common sexually transmitted infection in the United States, according to Centers for Disease Control and Prevention(CDC) around 20 million people are infected with HPV and additional 6.2 million people are newly infected every year. According to National Health and Nutrition Examination Survey in 2003-2004 among sexually active women (57% of 14 to 19 years and 97% of 20 to 59 years) HPV was highest prevalent in youngest age group (40% of 14-19 years and 50% of 20-24 years). Infection rates decrease after age of 24 years. There are more than 100 types of HPV viruses out of which 40 cause genital infections. Out of
What is HPV ? HPV is an acronym for Human Papillomaviruses , which is a group of over 150 different viruses . It is a sexually transmitted disease , that affects about 14 million people annually , usually people who are 20 - 25 . Where about 39,800 of those people have developed HPV associated cancers . HPV does not show specific signs or symptoms , making it easier for people to infect each other ( because they are unaware ) as well as making it harder to treat before it is too late . HPV causes genital warts and cancers such as cervix , vulva , vagina , anus , penis , rectum , and oropharynx ( cancers of the back of the throat , base of the tongue and tonsils ) .
Cervical cancer is formed in the tissues of the cervix, an organ that connects the uterus and the vagina. Virtually all cervical cancers are caused by Human papillomavirus (HPV) infections (Schiffman et. al., 2007). HPV is the most common sexually transmitted infection in the United States. According to the CDC, 75% of sexually active people aged 15-49 have the infection at some point in their lives. (CDC). Because HPV infection is usually asymptomatic, infected people do not know exactly when they get the infection. In most cases, the body is able to fight off the virus before any symptom. However, health problems such as genital warts and cancer may
The human papillomavirus is a type of virus that is spread through skin to skin contact with an infected person. It is very common. In fact, it is estimated that 20 million people in America have been infected with the HPV virus. This virus may not produce any symptoms.
The epidermal growth factor receptor (EGFR) is the cell-surface receptor for extracellular protein ligands. EGFR family has four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/c-neu, Her 3 and Her 4. Mutations affecting EGFR expression or activity could lead to cancer.
Causative Organism(s): Human papillomavirus known as HPV is a Papovavirus that is transmitted sexually. It is in fact one of the most common sexually transmitted disease in the United States, it comes in hundred different forms and affects the body in different ways. Some forms of it can cause warts while others may cause cervical changes that may lead to cancer (4). HPV can infect both man and woman but only causes cancer in females. Although HPV seems to have a more severe effect on women than men it still places both in danger. Men can unknowingly be carriers of the virus that can affect the woman severely, therefore both men and women have to take responsibility to decrease the spread of HPV (5). HPV is a small unenveloped virus with
Almost all sexually active people will get human Papillomavirus ( HPV) at some point in their life. Papillomavirus is a viral infection that is contracted via skin contact. Papillomavirus has multiple strains that can affect the genital area, skin, cervix, anus, mouth and throat. The degree of virulence of HPV depends on the on the strain that the person is infected with. Once a person has Papillomavirus there is no cure. However there is vaccines for preventive measures of certain strains.
Aberrant expression of p16INK4a, either high or low, is found frequently in human cancers (Table 1). In colon cancer, two different patterns of p16INK4a overexpression have been reported. The ﬁrst pattern is related to senescence in serrated adenomas, which have malignant transformation associated with p16INK4a downregulation (Refs. 138, 139). The second pattern is characterized by a very low p16INK4a immunostaining in normal mucosa, with a progressively higher expression in aberrant crypt foci, non-serrated adenomas, primary carcinomas and metastatic tumors (Ref. 87). A similar pattern was observed in skin cancer where p16INK4a expression increases from relatively low levels in pre-malignant lesions to high levels in in situ and inﬁltrating carcinomas (Ref. 140). In breast cancer, p16INK4a was negative or low in normal ductal epithelium, but a progressive increase was found in benign lesions and carcinoma (Refs. 88, 89). Increased nuclear p16INK4a protein expression compared with normal epithelium has been reported in pre-neoplastic and tumor tissues of the gallbladder (Ref. 141). Therefore, inactivation of
The Human Papillomavirus known as HPV is a very common virus. There are more than 100 different types of HPV and some affect the genital area. The virus is transmitted by skin to skin contact and by sexual intercourse. A lot of us, women especially will be infected with the virus at some point in our lives. The education that it is out there is to create more preventive measures the more we are inform about the virus the more we will be aware of what it can do. There is very little knowledge about how it can be prevented. Knowing that we are all exposed to the virus women and men we have to educate ourselves about what HPV can cause, how to reduce the risk of getting HPV, and how HPV affects the male population.
There has been many cases reported a year of people infected with various sexually transmitted infections. There are number of STI’s that are known to be common due to how often it’s contracted, tested, reported and treated. Currently, one of the main STIs that have become more common and is a major public health concern in the United States is the Human papilloma virus, also better known as HPV. Human Papilloma virus (HPV) has created a rapid spread among many individuals who have become exposed due to sexual contact with those who are infected. HPV is linked to many cancers, commonly cervical cancer among woman. HPV
The Human Papillomavirus also known as HPV is the most common sexualy transmitted infection. Currently there are millions of people in USA with HPV. It’s so common, nearly sexually active people get HPV at some point in their lives. Doctor’s now use a vaccine to prevent HPV. Alot of people don’t know they have been infected because it may take years to have any signs or symptoms.
Cervical cancer is the third leading cancer and fourth cause of cancer-related mortality in women (Jeronimo, Bansil, Lim, Peck, Paul, Amador, & Asthana, 2014). Eighty five percent of cervical cancer incidences occur in developing countries that do not have adequate cervical cancer screening or treatment programs (Jeronimo et al, 2014) Cervical cancer is a preventable disease caused by the oncogenic strains of human papillomavirus (HPV) infection (Boggan, Walmer, Henderson, Chaktoura, Mccarthy, Beauvais, & Smith, 2015). These high risk oncogenic HPV strains cause almost every case of cervical cancer.