HIV Related Kaposi Sarcoma - Essay Example

? HERPESVIRIDAE - Herpesviridae Epidemiology: During most of the 20th century Kaposi sarcoma wasnot a common cancer and its prevalence was limited to Mediterranean population only with mostly affecting the male patients. But later in the 1960s, cases in children were reported in some of the African countries (Sullivan et al 2006). Epidemiologically, Kaposi sarcoma can be divided into four types that are characteristically prevalent in different parts of the world. These four forms include classic, endemic, post-transplant or iatrogenic and HIV related Kaposi Sarcoma (Boshoff et al 2001; Eto et al 1996). The classic type is more prevalent in the European and Mediterranean countries and mostly affects the older patients. Classic Kaposi sarcoma is more common in the male population in comparison to the female population with a 3:1 ratio (Franceschi & Geddes 1995). The endemic form, also known as non-HIV related Kaposi Sarcoma, is more common in the African countries and was evident even before HIV appeared on the horizon. This form of Kaposi sarcoma is more lethal and progresses aggressively than the classic form. As predictable, prevalence of HIV related Kaposi sarcoma shows a linear relationship with the incidence of HIV infection. In UK, the classic type is the most prevalent form of Kaposi sarcoma. As it was evident in a retrograde study (Grulich et al 1992) conducted to analyse the epidemiological prevalence of Kaposi Sarcoma, the incidence of this cancer was very low in UK and Wales as compared to other western countries. It is estimated that the incidence rate in UK during 1970 and 1980 was about 20% lower than that registered in the United States (Biggar et al 1984). The retrospective analysis of 68 patients, who were found to be affected with Kaposi sarcoma during the period of 1971 to 1980 in UK and Wales, showed an interesting link. Most of the affected patients were not the natives born in England or Wales but were immigrants born outside in other countries. In depth research of those individual revealed that the geographic distribution of their country of origin corresponds to the pre AIDS region of Kaposi Sarcoma. This may highlight the fact the actual incidence of Kaposi sarcoma may be even lower in UK and Wales than was registered during the period of 1970 to 1980 (Grulich et al 1992). Pathogenesis: Kaposi Sarcoma was highlighted in the recent decades due to its association with Acquired Immuno-deficiency Syndrome (AIDS). It is believed to be the most common form of cancer evident in AIDS affecting approximately 15 to 20% of these patients (Chang et al 1994). But HIV alone is not responsible for the pathogenesis of Kaposi Sarcoma and an infective aetiology is suspected which plays a key role along with immuno compromised conditions. Kaposi Sarcoma associated Herpes Virus (KSHV) or Human Herpes virus 8 is the main infectious agent in the development of Kaposi sarcoma (Ganem 2006; Changet al 1994). The disease was first described by Moritz Kaposi and hence it was named after him. The word sarcoma is a misnomer in this case as the tumour was initially thought to be mesenchymal in origin. But eventually as the microscopic advancement revealed the inner depth of tissues, its pathogenesis became more evident and it was clear that the Kaposi Sarcoma lesion composed of different types of cells. The exact origin is still not clear but it has been proposed that it may arise from lymphatic endothelium (Beckstead et al 1985). During the development of the tumour, the lesions represent variable stages of the disease. The reddish patchy lesion signifies the beginning of the lesion with no mass yet evident on the skin. This lesion is still intra dermal and the red colour is due to new blood vessels formation, neovascularity, and red blood cell accumulation which is a prominent feature early in this disease. This is in contrast to the other tumours where angiogenesis begins at later stages of tumour progression. The elongated ‘Spindle’ shaped cells are the hallmark of these lesions. Further progression is characterised by plaque and nodular stages. Inflammation is also usually present with infiltration of inflammatory cells are evident under the microscope. Kaposi Sarcoma associated Herpes Virus (KSHV) plays a critical role in the development of these spindle cells (Regezi et al 1993). There are certain molecules, mostly protein that are encoded by various viral genes of Human Herpes Virus 8 and stimulate the proliferation and unregulated growth of cells that give rise to Kaposi Sarcoma (Sullivan et al 2008). It is believed that these molecules interfere with p53, the tumour suppressor protein, responsible for the controlled cell division (Friborg et al 1999). Viral G protein is also well known in activating various signalling pathways that ultimately leads to expression of Vascular Endothelial Growth Factor (VEGF) which is responsible for angiogenesis. Additionally, G protein inactivates the transcription factor and antiapoptotic protein nuclear factor that results in the blockage of transformation (Sullivan et al 2006). KSHV and AIDS are both responsible for the development of Kaposi Sarcoma. There is a possible explanation for this co-occurrence of these two diseases in this malignant condition. AIDS patient have extremely low levels of T cells which play a key role in the defence against KSHV. Therefore many studies have been conducted to support this hypothesis. It has been observed that AIDS patient affected with KSHV do not have the typical T cell proliferation response to KSHV (Guihot et al 2006). Properties of Herpesviridae and Subfamilies: There are over 100 different viruses under the broad family of Herpes viridae. The vast diversity is evident in the DNA arrangement and base sequence of these viruses (Roizman et al 1991). Moreover, they have a common ability to remain latent in their respective hosts. These virions consist of four layered structures. The innermost layer, core, is surrounded by capsid which is enclosed in the tegument layer. The outermost layer is called envelop. DNA is situated in the core in the form of an entangled ball associated with core protein that resembles a doughnut (White et al 1994). Envelop is studded with many glycoprotein structures that are the key factors for adhesion and attachment on the surface. Many different proteins are encoded by the DNA that aid in the survivability and pathogenesis of the virus. There are three subfamilies of Herpesviridae based upon the biological properties that include alphaherpesvirinae, betaherpesvirinae and gammaherpesvirinae (Roizman et al 1991). This family is further classified into different subfamilies which consist of the common viruses that infect the humans. Alpha group consist of Herpes Simplex virus both type 1 and type 2 and varicella zoster virus. These group members can remain dormant in the sensory nervous system and are notorious for their latent infections in the sensory nerve ganglia. The Betaherpesvirinae subfamily is comprised of HHV-6 and human cytomegalovirus. Their growth is relatively slow in the host cells and they form big multinucleated cells and it is due to these properties that the name is given to the virus. Epstein-Barr virus and HHV-8 belong to the third and last subfamily of gammaherpesvirinae. 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