The Early Viral Genes ( E6 And E7 )

HeLa cells have had a positive influence on medicine in many ways including with giving us knowledge about the human papillomavirus (HPV) DNA and HPV18-positive. HeLa cells have been linked to changes in microRNA expression. Since HPV18 has been associated with very aggressive adenocarcinomas, this finding may explain why Dr. Gey was surprised by the prolific growth of HeLa cells in culture. Routine Papanicolaou smear screening may not detect rapidly progressive cervical carcinomas; the new HPV vaccine holds the promise of preventing these tumors. (Hutchins).

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).

Cancer is a disease caused by an uncontrolled division of abnormal cells. The DNA sequence in cells can be changed as a result of copying errors during replication. If these changes whatever their cause are left uncorrected, both growing and non-growing somatic cells might gain many mutations that they could no longer function. The relevance of DNA damage and repair to the generation of cancer was obvious when it was recognized that everything that causes cancer also cause a change in the DNA sequence. Tumor suppressor genes are protective genes and normally they limit cell growth by monitoring the speed of cell division, repair mismatched DNA and control when a cell dies. When a tumor suppressor gene is mutated cells grow

Human papilloma virus will cause almost all cases of cervical cancer, and therefore is the highest risk factor. There are many factors that will determine if HPV will lead to cervical cancer, HPV directly affects and transforms either or both the deepest layer of the mucous epithelial cells and more superficial layers. Targeting the receptors found in the layers of the stratified squamous epithelium. This is where the virus will proliferate into more differentiated cells to spawn offspring virus. The virus replication is what causes the skin characteristics of a wart. With the help of a pap smear, we are able to investigate if cervical epithelial cells are healthy and normal or determine which point in dysplasia they are at in transforming to cancerous cells. The HPV virus does not need a host to survive, and can survive in low and high temperatures.

Human Papillomavirus (HPV) is a double -stranded deoxyribonucleic acid (DNA) virus that only infects humans with an attraction to both cutaneous and mucosal surfaces such as the cervix, anus, tonsil, and oropharynx (Clark, 2013). HPV is a type of oncogenic virus that goes into the cells and can cause several diseases. Over the years, research has surfaced connecting genital HPV to several types of cancer. There are over a hundred strains of HPV but the most high risk strains, 16 and 18, have been shown to cause vulvar, vaginal, anal, and the most concerning, cervical cancer (Chan, Ng, & Wong, 2012). Genital HPV

Human papillomavirus (HPV) is made up of double stranded DNA with a capsid. Their viral genome is consisting of such as early (E) gene like E6 and E7encodes for oncoproteins and late (L) gene such as L1 and L2 encodes for structural proteins like capids. There are more than 100 different types of HPV identified and they generally infect around cutaneous or mucosal areas. HPV viral genome can be categorized into low risk (LR) and high risk (HR). High risk types such as HPV-16 and -18 are ones that can develop into cancer and other tumors mostly in genital area or a head and neck squamous cell. Low risk types such as HPV-6 and -11 are more frequently found I larynx or genital area (Klozar et al., 2010). Therefore, careful evaluation such as risk factors, or possibly a new vaccination to prevent against HPV related to oropharyngeal SCC should be questioned in public health

Human Papilloma Virus (HPV) is one of the most common sexually transmitted infections in the United States. HPV belong to a family of viruses that cause cell changes in the epithelia resulting in benign skin lesions called warts and verrucae. Type 6 and 11 cause warts and are included under the low risk HPVs,Types 16,18,31,33,45 cause cervical cancer and are included under high risk HPVs(CDC,2014). The virus affects the skin and mucous membrane especially of the reproductive organs. Cervical Cancer and other Ano-genital cancers are seen in women with persistent genital HPV infection. HPV that affects the

HPV works like all other viruses, the virus inserts its DNA into the cell and the cell begins to produce the protein that the virus encodes. HPV attacks epithelial cells, epithelial cells are what make up the outside layer of skin on the body, including the cervix. In types 16 and 18 the creation of HPV proteins interferes with the cell’s ability to prevent excessive growth. The cell grows uncontrollably and does not die. This excessive growth is manifested as a precancerous

It is estimated that 79 million Americans are currently infected with a strand of Human Papilloma virus (HPV), and that 14 million Americans become infected annually (CDC HPV Questions and Answers, 2016). HPV was discovered in 1979 when HPV-16 and HPV-18 were found to be linked to cervical cancer (Hausen, n.d.). Every year 27 million Americans get cancer from HPV (CDC What Is HPV, 2016). Cancers associated with HPV whose rates were larger than the mean U.S. rate (11.7 per 100,000) were located in the Southern United States(CDC MMWR, 2016).

Eukaryotic cells are regulated by the cyclin-dependent kinases also known as the CDK. The CDK is a bunch of protein kinases, and help the order and movement of the cell cycle. (Serrano) The first proteins are responsible for the destruction of the cell. They tags the repressor molecules and go to work. The second proteins binds to the host proteins and traps it. ("Karyotyping Cancer Cells.") Cancerous HeLa cells use a CDK4 and are not associated with the p16 tumor protein. Another difference in proteins is that HeLa cells have the papillomavirus E6 and E7 proteins which deal with the life cycle. HeLa cells contained a protein Mr 16K which was not found in normal cells. (Serrano) The HPV virus goes into healthy cells and infects them with proteins that change the way the cell cycle

The E6 and E7 proteins play and important rule in oncogenic property of human papillomavirus that can cause anogenital cancers as their high risk factor and warts as their low risk factor. E6 AND E7 proteins promote cell growth by inactivating the tumor suppressor proteins P53 and PRb (5).

Moreover, preliminary data show that deletion of RRM2, but not the RS domain, results in decreased MALAT1/SRSF1 interaction and that MALAT1, SRPK1 (SRSF1-specific kinase), and SRSF1 also form a complex. This scientific literature and empirical evidence regarding the relationships between SRSF1, p53, OIS, and MALAT1, when taken together, have led us to our central hypothesis that MALAT1 overexpression disrupts the interaction between the RRM2 and RS domain in SRSF1, subsequently impairing SRSF1 RS domain phosphorylation and thus its nuclear translocation. This change in subcellular localization, in turn, destabilizes p53, leading to loss of OIS in HPV-negative cervical cancer (HNCC). Our goal is to examine the differential expression and biological importance of MALAT1 in HNCC and its consideration as a useful therapeutic target.

As mentioned earlier, HPV is a non-enveloped, icosahedral capsid, double-stranded circular DNA virus (Morshed, 2014). Infection of HPV occurs in the cervix, glans of the penis, penile shaft, scrotom and anal verge by interactions with “host cell surface receptors such as heparin sulfate proteoglycans and alpha-6 integrins” (Schafer, 2015; Letian, 2010). Most studies suggest that HPV16 enters the cell via clathrin-mediated endocytosis (Day, 2003, Bousarghin, 2003, Smith, 2007, Hindmarsh, 2007), however, notably, a few contradictory studies suggest that HPV16 is clathrin and caveolaen independent (Spoden, 2008). Once the virus has entered the cell, it then un-coats and delivers its genome (8 genes) to the host cell nucleus to be expressed. These eight genes are named for when they are expressed during the virus’s occupation of its host: early (E) and late (L). The proteins E1, E2, E4 and E5 play an important role in genome replication (Beutner, 1997; Gnanamony, 2007) while E6 and E7 are oncogenes and are capable of causing cancerous growth of host cell (Gnanamony, 2007; Sikorski, 1998). E6 is thought to complex with p53 which is a cellular tumor repressor (Werness, 1990); when E6 complexes with P53, it is thought to promote the degradation of p53 via the ubiquitin pathway (Schffner et al., 1990). This degradation of p53 contributes to the oncogenic potential of high-risk HPVs (Stewart, 2005, Thomas, 1999). Crook (1991) showed that E6 can bind with p53 without degradation

HPV-16 DNA was found to be present in 50% of all cervical cancer biopsies while HPV-18 was found to be present in 20% of the cases. These figures proved that HPV-16 and 18 play an important role in cervical cancer development.

Human Pappillomavirus is most commonly known as HPV and is the most common sexually transmitted disease with 360,000 new cases reported annually (Maurer 2016). HPV is a virus and it should be noted that it is not a singular virus. It is made up 100 viruses that are closely related. The difference however, is the severity of the specific strands of HPV. It is of the Family- Papillomarviridae, the Genus- Alphapapillomavirus and the species - Human Papillomavirus . The DNA which characterizes HPV is distinctly circular shaped, double chain and within it holds an estimate 8000 base pairs. This virus is located within the body specifically inside of thin, flat cells which are scientifically known as epithelial cells. Epithelial cells are