“Human Herpes Virus-8 (HHV-8) and Kaposi’s Sarcoma (KS)”

Human herpes virus (HHV-8) poses a challenging task for researchers determining its role in Kaposi’s sarcoma (KS). People with KS are distinguished by their placement in four categories. The first category consists of elderly males of Mediterranean or Eastern European Jewish descent. The second category consists of individuals of all ages from Africa. Neither one of these categories is associated with immune deficiency or known environmental factors. The last two categories are associated with organ transplants or HIV-1. In all forms of KS males are predominantly affected.
Kaposi’s Sarcomas are known to harbor cells known as spindle shaped cells (SC). The spindle shaped cells are associated with abnormal blood vessel development and blood leakage. Although, the SC is the most frequently encountered cell in KS tumors it is undetermined if they are neoplastic cells or hyperproliferating cells or an altered cell induced by cytokines (INF-).
Although, it is easy to believe that all cells in a tumor are neoplastic, evidence suggests otherwise. There are three characteristics that are present in all KS cells whether they are neoplastic or not. The first is absence of a histologically distinguishable neoplastic cell. The second is the lack of usual chromosomal abnormalities. The last is a combination of three features angiogenesis, inflammation, and proliferation.
The one factor that brings the four categories of people infected with KS is HHV-8 found in KS tissues. Although, HHV-8 is thought to be connected to KS, HHV-8 itself has very low risk factor for KS development. Most reports on KS indicate a 2% to 10% prevalence of HHV-8 in the world, but in the U.S. there is thought to be a 5% prevalence among men according to a 1970s baseline incidence of KS. In relation to HIV-1 incidence of KS increases by a factor of 20,000 to 50,000 times with the presence of HHV-8.
It is postulated that HIV-1 infections promote HHV-8 replication indirectly by suppression of host immune systems. KS is thought to begin with micro-vascular lesions mediated by different environmental factors for each of the four categories of KS. One of these factors is abnormal cytokine production; in HIV-1 associated KS, this includes an increase in inflammatory cytokines, such as IFN , TNF , and IL-7 that are enhanced by Tat of HIV-1. Tat which is essential for HIV-1 replication is released and taken up by other cells, where it inhibits T-cell proliferation and promotes abnormal cytokine production, adhesion, and growth. Tat interaction with cells is mediated by a RED motif (cell binding motif), which is represented in HIV-1 but not in HIV-2. Thus, KS is less frequently associated with HIV-2.
HHV-8 is thought to be linked to KS by a homologue of a G-protein coupled receptor encoded by ORF 74 (open reading frame 74). This homologue of G-protein is expressed in some KS tissue, which in turn induces angiogenic cytokine such as VEGF (vascular endothelial growth factor). Thus, expression of the homologue leads to cell growth. Although, VEGF is expressed in KS tumors ORF 74 is not expressed in all KS tumors, which suggests a more complex pathway to expressing VEGF than simply expressing ORF 74.
In vitro growth promotion of endothelial cells infected by HHV-8 with results that infected cells are more responsive than uninfected cells to high VEGF. Thus, leaving doubts if whether these effects can be called transformations or immortalization. If HHV-8 is discovered to be a transforming virus inhibition of replication should have no effect on neoplastic cells. Thus, this would be consistent with the reasoning that not all cells of KS tumors are neoplastic.
The detection of HHV-8 DNA sequences in virtually all patients with KS, with or without HIV infection, has allowed researchers to hypothesize a causal role for this virus in the pathogenesis of KS. Studies have shown that homosexual men are more likely to have anti-HHV8 antibodies than individuals at risk with non-sexually transmitted HIV infection and that HHV-8 seroconversion, the presence of antibodies against the HHV-8 latency-associated nuclear antigen, appears before the clinical onset of KS. The virus has also been consistently detected in primary-effusion B-cell lymphomas and in Castleman’s disease.
The extent to which HHV-8 is a universal infectious agent is still unclear. It is not known whether HHV-8 may also be transmitted by routes similar to