Fusion and Fusion Inhibitors -- Understanding the News
It was in May of 1996 that scientists first announced having found Fusin, a cofactor for HIV entry into the T-cell. Women Alive reported the new findings in the winter issue of that same year. Now, almost two years after its first discovery, Hoffmann-La Roche, the maker of Saquinavir, and Progenics Pharmaceuticals, a New York based company researcher of HIV co-receptors, have announced a collaboration to find a drug that will inhibit fusion. It may be time for a little update on the subject.
Reverse-Transcriptase Inhibitors (such as AZT and Nevirapine) and Protease Inhibitors (such as Crixivan) work by interfering with the replication process of the virus. This process takes place inside the human T-cell or CD-4 cell. No drug of either category is able to keep HIV from getting into the CD-4 cell in the first place. For that, a new class of drugs would be necessary: drugs inhibitors of proteins that HIV uses to attach itself to the cell.
The main protein used by HIV is CD-4, after which the cell is named. This protein is of vital importance to the functioning of the immune-system. As such, it can not be inhibited, much to the contrary, it must be protected.
Scientists have long suspected that an additional protein, a co-receptor, also had to be used by HIV to enter the T-cell. The major break through happened when they were finally able to identify one such substance. That's when Fusin was found.
Fusin, also called CXCR4, was named after Fusion, which is the process of attachment of HIV to the T-cell. After its discovery, a number of other co-receptors were found.
In an abstract presented at the 5th Conference of Retrovirus and Opportunistic Infections this February in Chicago, IL, scientists indicated that the most used co-receptors are CXCR4 and CCR5, being the latest one used exclusively by HIV in early stages of infection (before development of p24 antigen). Other identified co-receptors, such as CCR2b, CCR3, BOB and BONZO, appear not to be used as much by HIV. (Abstract 281 / Session 40)
According to the research, to date, CCR5, is the most largely used HIV co-receptor. The data also corroborates findings from genetic research which studied long term slow progressors. They are twice as likely to have just one gene (heterozigote) with instructions for production of CCR5 than the control group, instead of having two such genes (homozigote). (Abstract 56 / Session 13)
All data indicate that inhibiting CCR5 is the key to halt the fusion process and keep HIV from entering the T-cell. CCR5 is a chemokine receptor. (The "CC" is an abbreviation related to its chemical structure.) This is exactly the substance that Roche and Progenics will start investigating. Over all, there is much reason for hope that we will be alive for the cure.
Although it is not clear when human trials will start, there is a lot of expectation in this direction of research.
For one, it may result in the last cocktail ingredient that will finally eradicate HIV in the human body. We can only hope!
On the other hand, it may drive HIV into using some of the other co-receptors and precipitate the evolution of a much more virulent strain of HIV.
Controlling HIV has never been easy but the more we learn about it the closer we get to the cure. Also, the speed of new findings increases with every new breakthrough, like what happened with the discovery of Fusin. Over all, there is much reason for hope that we will be alive for the cure.
This article was provided by Women Alive. It is a part of the publication Women Alive Newsletter.