Regardless of its effect on EBV infection the
Regardless of its effect on EBV infection, the chemokine system has been found to be regulated in both nasopharyngeal cancer and Hodgkin lymphoma. As such, Hodgkin and Reed–Sternberg (HRS) cells from Hodgkin lymphoma and nasopharyngeal carcinoma cells have been shown to express CXCL8 and CCL17. Furthermore, Hodgkin lymphoma cells express high levels of CXCL9, CXCL10, CCL3, CCL5, and CCL11.
EBV-Associated Diseases Primary EBV infection often occurs in young immunocompetent children and is asymptomatic or present with nonspecific mild symptoms. However, given that EBV was originally identified in Burkitt\'s lymphoma cells and has the unique ability to transform resting B cells into highly proliferating lymphoblasts, it is not surprising that this virus is associated with a number of cancers in both immunocompromised and immunocompetent patients. In addition, EBV has been associated with autoimmune diseases involving infected B cells (see Table 3 for an overview of confirmed EBV-associated diseases).
Drug-Target Potential 7TM receptors and in particular class A receptors to which the 7TM receptors mentioned in this review belong, are highly druggable molecules. Approximately, 35% of all currently marketed drugs target class A 7TM receptors. There is no specific antiviral treatment for EBV. Current treatment strategies for EBV-associated lymphomas include B cell SR 1664 sale (rituximab, chimeric, and monoclonal antibody against CD20), reducing immunosuppression, EBV-specific CTL infusion, and chemotherapy for PTLDs; and anti-HIV treatment for HIV-associated lymphomas.158, 159 The use of rituximab in particular has dramatically changed the overall survival of PTLD patients, but a strategy directed specifically against EBV-infected cells and genes, which play a role in the EBV-mediated pathogenesis, could likely reduce the incidence of malignancies. As such, BILF1 constitutes an obvious target as it plays a role for EBV immune evasion56, 61, 62 and has oncogenic properties both in vitro and in vivo. EBI2 has been shown to have proliferative effects ex vivo and in addition, the receptor is upregulated in PTLDs. Though the role of EBI2 in EBV life cycle is still uncertain, the aforementioned knowledge suggests that EBI2 could play a role in EBV-mediated lymphoma development and therefore EBI2 constitutes another potential drug target. Finally, the chemokine expression pattern is skewed in both Hodgkin lymphoma and nasopharyngeal carcinoma meaning that inhibition of some chemokine receptors could prove beneficial in the antiviral treatment strategy.
Oxysterols are oxygenated derivatives of cholesterol produced by the oxidation by the CYP family of enzymes in the cells and falls in the bile acid synthesis or steroid synthesis pathway. Few oxysterols such as 7-hydroxy and 7-keto are also known to be produced in vivo by non-enzymatic radical oxidation mechanism. Although found in very low concentrations in most mammalian tissues, oxysterols play a crucial role in cholesterol and fatty acid metabolism, regulation of immune response and are also believed to be mediators in neurodegenerative disorders. While oxysterols were most extensively studied for its potent ability to mediate feedback regulation of cholesterol biosynthesis, some early investigations showed that the enzymes involved in its syntheses were highly upregulated in macrophages and dendritic cells—an indication of possible roles in immune related functions., Subsequent research has shown that oxysterols have a broad range of roles in innate and adaptive immune responses. For example, 25-hydroxycholesterol (25-HC) is induced in macrophages by type 1 interferon (IFN) signaling and has broad ability to prevent viral entry, replication and budding., In addition to the pro-inflammatory effects, many studies show that, 25-HC also mediate the anti-inflammatory effects downstream of the IFN pathway.