Cloning, Highly Effective Expression Of RANTES And Its Characterization In SARS-CoV And HIV Infection

Learned from the extraordinary progress accumulated during the past 20 years, greatly understanding the change of chemokine, chemokine receptor and may have critical implications for explore a full, precise description of the pathogenesis in allegic inflammation, infectious diseases and automatic immunologic disorders. RANTES is a typical CC chemokine and a powerful attracxin. It mediates the trafficking and homing of classical lymphoid cells such as T cells and monocytes, but also acts on a range of other cells, including basophils, eosinophils, natural cells, dendritic cellls, neurocytes and mast cells. So, RANTES has versatile effects and potentially relevant in a range of inflammtory disorders due to its chemotaxis.RANTES is one of natural ligands of CCR5. It attracted particular attention when it was demonstrated, alonged with two other chemokines, to be a potent inhibitor of HIV replication in vitro, the three chemokines all bind to the CCR5 receptor on the surface of CD4+ T cells, and this recrptor is also the means by which HIV gains entry to the cell. In the course of sutdies that explored the potential use of RANTES in HIV therapy, additional and intriguing features of RANTES biology have emerged. The activity of the chemokine RANTES can be divided into three parts: leukocyte activator; inflammation modulator and immune modulator. And the effects of RANTES can be separeted into two groups according to its concentratrion: at low concentrations, RANTES acts in a monomeric (or dimeric) form directly on its specific chemokine receptors; at high concentrations, it self-aggregates and acts through interactions with cell-surfaceglycosaminoglycans (GAGs). Once RANTES binding to its receptor, it plays a key role in promoting leukocyte infiltration to sites of inlammation and immune response to infecton. Increased RANTES expression has been associated with a wide range of inflammatory disorders and pathologies, including infectious disease, allergic disease and automatic immunologic diseases.In 1995, RANTES was shown to be the most potent member of a trio of CC chemokines released by CD8+ T cells that were able to suppress the replication of non-syncitium-inducing (NSI) HIV-1 strains in vitro. Soon thereafter, several research groups found a consistent opposite result that RANTES could enhance HIV replication in some circumstances in vitro. The contrating effects of RANTES on HIV replication in vitro were contributed to different exprimental conditions, such as the concentration of RANTES, the cell line and HIV strain used. The basis for those explanation was that RANTES binding to different receptor exerts paradoxical effect. These observations raise several questions: what is the relationship between endogenous RANTES and the course of HIV infection? How about its therapeutic potential as a treament of HIV infection?By collected the information regarding cheokines assocaited with diverse viral infection, William found that respiratory viruses commonly induce inflammatory chemokines such as macrophage inflammatory protein-1 a (MCP—1 a ) and RANTES, which can amplify inflammatory responses leading to immunopathology. To be important, the major chemokine responses to these respiratory viruses may be determined by the target cell, and less by the specific identity of the pathogen. Increased RANTES expression is one of the features of inflammatory response which appears within the airways of inflammatory airway disorders including allergic asthmatics, and elevated RANTES promote leukobyte infiltration to site of inflammation. In a mouse model with mouse hepatitis virus (MHV), a coronavirus, results in central nervous system damage, pathogenesis involves chemokine receptor CCR5 and the cytokines released by CD4+ T cells. Severe acute respiratory syndrome (SARS) is a newly recognized illness associated with infection from a novel coronavirus (SARS-CoV). Immunopathology plays a role in tissue damage, and cytokines are responsible for some signs of disease. It is reasonable to hypothesize, however, on the bai...