Human Papilloma Virus ? a Review

by Rachel on April 23, 2010

Human Papillomavirus – A Review Sameera Mohotti (BSc, MSc, MD (MA)) INTRODUCTION HPV is one of the most common sexually transmitted viral diseases. There is It is estimated that 80% of sexually active adults with one or more types of genital HPV at some point in their lifetime have been infected. The prevalence of HPV is increasing worldwide. Although difficult, the overall prevalence estimate of HPV infection is assumed that the prevalence could be as high as 20 million (Revzina 2005). The total cost of health care to early detection and treatment of cancer of the cervix associated with the United States amounted to about a year 6000000000 (Koutsky, 1997). A U.S. study of HIV prevalence study Revizina et al found that the prevalence of HPV is among students, women, clinics for sexually transmitted data from hospitals in Australia indicate a prevalence of 4-13% in STD clinic attendants after the initial infection, HPV infection establishes a latent can occur from periodic symptomatic recurrences (Revzina 2005) (Armstrong, 1986). The main objective of this study was to evaluate the current literature on the types of HPV, symptoms and their pathogenesis. Spectrum of HPV More than 200 types of HPV have been classified according to their DNA sequence homology. 85 HPV genotypes are well characterized. HPV can be high risk and low risk HPV cons are grouped according to their association with cancer and their precursors. High-risk HPV have a strong potential oncogene. This group includes serotypes 16,18,31,33, 34, 35,39,45,51,52,56,58,59,66,68. oncogenic potential HPV low risk and less often leads to the formation of low-grade precancerous lesions. This group includes Serotypes 6, 11, 42, 43, 44 This difference in ability to induce malignant transformation is the functional difference of E6 and E7 saw the two groups (Burd 2003, Longworth and Laimins 2004). Although many HPV infections are sub clinical infection leads HPV usually symptomatic lesions. Each HPV serotypes infecting certain parts of the body responsible for several types of lesions. Under the current classification (Bethesda System) of the HPV lesions, there are three main groups. You are anogenital warts, low grade squamous intraepithelial lesions (cervical and anal intraepithelial neoplasia and mild dysplasia) and high quality intraepithelial lesions (moderate and severe dysplasia). Cervical cancer / Anal / vulva penis / usually develop from squamous intraepithelial lesions (University 2001). Genital warts (foci of epithelial proliferation of keratinocytes infected with HPV) appear as lumps or growths in the genital area. This is one of the most common clinically recognized manifestations of genital HPV disease. They are usually found in the vulva, urethra, anus and vagina and cervix. Warts are highly contagious and sometimes lead to cervical cancer Women or penile cancer in men (Lacey, 2005). The presence of abnormal cells on the surface of the skin is called dysplasia. Dysplasia is not cancer, mild dysplasia is likely to be resolved. However, a slight, moderate and severe dysplasia could be a cancer if they have not recognized and treated in its early progress. Studies show that young low dysplasia and high grade squamous intraepithelial lesions, high risk of progression to high-quality cervical abnormalities (Wright, Pinto et al. 2004). BASIC VIROLOGY HPV is a nonenveloped DNA viruses, double-stranded circular with a diameter of 5 Nm the 5th The genome is approximately 8 KB in size and packed in an icosahedral capsid consisting of 72 capsomers. Capsid is composed of an outer protein coat, which is composed of two capsid proteins L1 (major) and L2 (minor) (Sapp and Volpers al. 1995). HPV genome is functionally divided into three zones. They are the region upstream regulator, the beginning and end of the Region. The upstream regulatory region includes the replication of the virus and also controls the transcription of certain sequences in the region earlier. The early region of the genome contains six open reading frames (ORF), designated E1, E2, E4, E5, E6 and E7. These encode proteins of viral replication, transcription and cell transformation involved. E6 and E7 regions are responsible for oncogenic properties of HPV. The region contains two ORFs and the end of that encode those proteins L1 and L2 structural, which is responsible for the production of capsid (Volpers Sapp, and al. , 1995). PRODUCTIVE HPV input gain of HPV in the host cell by the basal layer of the epithelium. In the first HPV infection exist as episome. It has been suggested that HPV-6 attaches to host cells about? Intergrin-6 in epithelial cells, where, how, fix HPV16 and HPV-33 cells by heparin sulfate surface of the host cell. The expression of genes with papillomavirus stages of differentiation of the epithelium and associated virus multiplies as it spreads through the natural maturation of epithelial cells (Giroglou, Florin et al. 2001). During virus replication, binds the E1 gene (E1 protein) to the origin of viral replication, and this result in the extra chromosomal replication of the viral genome. The E2 gene product (protein E2) down-regulates the E6 and E7 regions to allow the normal differentiation of the cell. The capsid genes L1 and L2 capsid protein synthesis and the allocations for each episomal DNA in a capsid protein. The gene product E4 (E4 proteins) with the maturation and release of virus particles papillomavirus (Burd 2003), (Longworth and Laimins 2004) connected. The results in productive viral stage papillary or flat lesions. Since the replication of the papilloma virus is associated with the differentiation of epithelial cells, such as lesions are superficial epithelial layers and medium would be a large amount of viral DNA containing formed. The accumulation of viral particles in the surface epithelial cells to cause koilocytosis cytopathic effect. This gives rise to koilocytes whose core is moved to the side with a hollow appearance of the cytoplasm. The virus particles are released to die koilocytes be postponed (zur Hausen 1991 Longworth and Laimins 2004). Pathogenesis of oncogenic HPV If a person is infected with HPV high-risk, it may take up to 20 years for Cancer changes appear. This persistence of HPV infection is necessary for malignant transformation of cells. In HPV-associated benign lesions, HPV DNA is usually located extra chromosome, where, as in cancers associated with HPV, HPV DNA was integrated into the rule in the host genome. Integration of high risk HPV DNA into the host cell disrupts the E2 region. This leads to the loss of normal E2 down-regulation of E6 and E7, which leads to the upregulation of HPV viral oncogenes both E6 and E7. The E6 and E7 gene products has the potential to destabilize the cell growth regulation and changes in the cellular environment in which they replicate (Jan MM Walboomers 1999 Yoshinouchi, Hongo et al. 1999; Burd, 2003). PRB and pRb-related proteins are important components of the cell cycle, as they take the transcription factor E2F, which is necessary for the functions of the cell cycle. If E7 proteins bind to pRB, pRB-E2F is complex disorder that causes the release of E2F. This disorder affects the normal functions of the cell. viral gene products E6 protein E6, which targets p53 immunosuppressive (low risk HPV types decreased p53 binding affinity). The p53 protein prevents cells from completing the cell cycle regulated and development of DNA repair genes are involved when there is no DNA damage. Another important function of p53 is a cell with DNA damage instructed to commit suicide. If the function of p53 is damaged, then these cells continue to divide and accumulate mutations that would lead to the formation of an inactivated tumor. If E6 binds to p53, E6 associated ubiquitin ligase catalyzes the degradation of p53 ubiquitin. This destroys the tumor suppressive properties of p53 (Syrjanen 1999; Ha and Califano, 2004). The ability of E6 and E7 gene products, p53 and pRb cellular functions lead to increased cell proliferation and genomic instability to disrupt. Finally, the cells accumulate DNA damage / mutations that can turn lead to the formation of cancerous cells fully. The low-risk HPV seem to be unable to integrate into the host genome. But the low-risk HPV serotypes 6, 11 in the chromosomal instability that can lead to accumulation of mutations of the events that transformed cancer cells form in turn lead to completely would result. In addition to contributing to the E6 and E7 protein function in methylation of viral DNA, activation of telomeres, humoral factors and cellular changes also immunogenic (Holowaty, Miller et al. 1999; Burd, 2003) . REFERENCES Armstrong, BK, Allen SC, Brennan BA, IA Fruzynski, NH de Klerk, Ed Waters, J. Mr Machin and Gollow M. (1986). “Time trends in prevalence of cervical cytological abnormalities Women attending a sexually transmitted disease clinic and their relationship to trends in sexual Activity and specific infections. “Br J Cancer 54: 669-75. Burd, E. M. 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(2005). “The treatment of diseases of genital human papillomavirus. Journal of Supplement Clinical Virology: Human papillomavirus 32 (Supplement 1): 82-90. Longworth, M. S. and L. A. Laimins (2004). “Pathogenesis of human papillomaviruses in differentiating epithelia. Microbiol. Mol Biol Rev 68 (2): 362-372. Revzina, N. V., J. and R. DiClemente (2005). “Prevalence and incidence of HPV infection among women in the United States: a systematic review.” Int J STD AIDS 16: 528-37. Sapp, M., C. Volpe, et al. (1995). Organization of the major and minor proteins of human papillomavirus capsid type 33 viral particles. J Gen Virol 76 (9): 2407-2412. Syrjanen, S. M. Syrjanen, J. K.. (1999). “New concepts on the role of human papillomavirus in cell cycle regulation.” Ann Med 31: 175-187. University, J. S. H. (2001). “Induced by HPV anal dysplasia: what we know and what we can do about it? (Online) Wright, J. D. A. Pinto, B., et al. (2004). “Atypical squamous cells of unknown significance in girls and women.” Obstet Gynecol 103 (4): 632-638. Yoshinouchi, M. A. Hongo, et al. (1999). “Analysis of the PCR multiplex Fitness human papillomavirus type 16 DNA in carcinoma of the cervix.” J. Clin. Microbiol. 37 (11): 3514-3517. zur Hausen, H. (1991). “Human papillomavirus in the pathogenesis of anogenital cancer.” Virology 184: 9-13.

Sameera Mohotti (BSc, MSc, MD (MA))

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