vMIP-II is the only known molecule to block all main co-receptors used by HIV to gain entry to cells (CCR5, CCR3, CXCR4 and US28). Full details of the research, carried out in a three way collaboration with the Geneva Glaxo Wellcome group and teams led by Dr Thue Schwartz in Copenhagen and Dr Paul Clapham in London, are reported in the September 12th issue of Science.
The research adds to the growing evidence that chemokine antagonists may lead to novel approaches to HIV therapy either to prevent initial infection or to slow down disease progression in an already infected patient. Importantly, this research shows for the first time that it is possible to block both types of chemokine receptor used by HIV with one molecule. "vMIP-II will help us understand the structural differences between these two types of receptors and may lead to the discovery of a small molecule that would block both receptors," said Dr Wells. HIV uses CCR5 as a co-receptor to gain entry to macrophages during the initial infection and asymptomatic phase of the disease. Later on, HIV mutates allowing it to gain entry to T cells through CXCR4.
Biologically, the virus appears to have optimised vMIP-II to block leukocyte recruitment to the site of Kaposi's sarcoma. HHV-8 is most probably using the novel chemokine to shut off the inflammatory response that would normally be associated with a tumour. This means it may also be a useful tool in diseases such as rheumatoid arthritis or asthma where the human immune system is abnormally activated or even as a means of understanding transplant rejection. It may also lead to useful anti-inflammatory agents for asthma and rheumatoid arthritis.