Science Daily (July 31, 2010)
Research by the Consejo Superior de Investigaciones Científicas (CSIC) and led by Mr Félix Goñi, director of the Biophysics Unit at the CSIC-University of the Basque Country Mixed Centre, has led to the development of a novel method of attack against the AIDS virus. The method involves creating a prevention system, i.e. an 'armour' in the cells that are likely to be infected and thus impede the virus from accessing them and starting to act on their immunological system.
The study, which appears in the journal Chemistry & Biology, published by Cell Press, lays down the bases of possible future pharmaceutical drugs that will enable combating the AIDS virus at its initial phase. Participating in the research, apart from Mr Goñi, was a team from the National Biotechnology Centre (CSIC-Universidad Autónoma de Madrid) and another from the Institute of Applied Chemistry of Cataloniaa (CSIC, Barcelona).
The research is based on the regulation of the fluidity of the cell membranes and seeks to avoid the phenomenon known as the fusion of membranes, a consequence of contact between the cell membranes and the membrane of the virus itself.
The membrane is the "coating" of the cell cytoplasm and which protects it from the outside, and which has a structure similar to that of the membranes of the AIDS virus. When both membranes come into contact, and due to the fact that the cell membrane is very "fragile," an orifice is created and fusion occurs -- and a route is opened for the AIDS virus to enter, connect to a specific "receptor" of the cell and commence its viral activity.
What the researchers are seeking with this study is to strengthen the membrane structure, making it more rigid, in order to avoid this fusion of membranes and, thus, the inoculation of the cell by the AIDS virus.
Practically all treatment for the AIDS virus currently being applied is based on halting the progress of the virus once it is inside the host cell. There is but one treatment, commercially known as Enfurvitide, which attempts to stop the virus actually entering the cell. The research published in Chemistry & Biology comes to the same conclusion, but by a totally different and novel route.
"For the cell membranes and the virus to come together and this orifice be opened to allow the entrance of the virus, the membranes have to have a certain degree of fluidity, of mobility. We discovered a procedure to make the cell membranes more rigid. This could well give rise to a new pharmaceutical drug which makes the membranes more rigid and impede the entrance of the AIDS virus. Instead of the membrane being flexible, a kind of armor is established which makes the cell impenetrable," explained Félix Goñi.
The research started three years ago and has employed various techniques in the field of chemistry and molecular biology.
At the Institute of Applied Chemistry of Catalonia (CSIC, Barcelona), Ms Gemma Fabriàs has synthesized the GT11 molecule by means of organic chemistry synthesis techniques. Mr Santos Mañes, from the National Biotechnology Centre, studied the viral infection of the cells, and from the Biophysics Unit at the CSIC-University of the Basque Country work has been undertaken at molecular level to demonstrate that there are changes in the rigidity of the membranes when the GT11 molecule is incorporated into them, and that when the membranes are more rigid the virus cannot fuse with the cell membrane and, thus, from penetrating the cell. A highly important role was also placed by Mr José Luis Nieva, from the Biophysics Unit, in studying this fusion of the membranes induced by the AIDS virus.
This scientific discovery by this consortium represents, in the opinion of Mr Goñi, "a completely new means for attacking the virus, and which makes this original."
"There is medication, and which is working very well, to avoid the propagation of the virus once it is inside the cell. But to impede this inoculation in the first place, only one product (Enfurvitide) exists, but this drug is based on a completely distinct principle. The idea of modifying the rigidity of the membranes is completely new and also demonstrating that, by equipping these membranes with greater rigidity, the AIDS virus cannot penetrate," stated Mr Goñi. This same strategy may well serve for other viruses with membrane, such as, for example, the flu virus.
Dihydrosphingomyelin Impairs HIV-1 Infection by Rigidifying Liquid-Ordered Membrane Domains.
Catarina R. Vieira, Jose M. Munoz-Olaya, Jesús Sot, Sonia Jiménez-Baranda, Nuria Izquierdo-Useros, Jose Luis Abad, Beatriz Apellániz, Rafael Delgado, Javier Martinez-Picado, Alicia Alonso, Josefina Casas, José L. Nieva, Gemma Fabriás, Santos Mañes, Félix M. Goñi.
Chemistry & Biology, 2010; 17 (7): 766 DOI: 10.1016/j.chembiol.2010.05.023
Link to Chem & Biol abstract