How HIV spreads from DCs
20.12.2012 - Spanish researchers have unraveled how HIV disperses throughout the body – and can block the process before it occurs.
In a previous publication with Swiss and German virologists, researchers headed by Nuria Izquierdo-Useros from the AIDS Research Institute IrsiCaixa in Barcelona discovered that the HI virus uses specific membrane lipids called gangliosides on their surface to enter dendritic cells (DCs) by modifying membrane fluidity. Based on these findings, they tried to make the DC’s membrane more rigid by using a dihydroceramide desaturase (Des-1) blocker, which they have filed for patent. The new approach seems promising because HIV has first to enter DCs to be passed to their target cells, the CD4 T lymphocytes, in a process termed trans-infection. Now, the Spanish team has identified the molecule on the surface of DCs that recognises and binds the gangliosides and allows HIV to be taken up by dendritic cells and transmitted to CD4 cells. The new study is published in the open access journal PLOS Biology.
In order to identify the precise molecule located on the membrane of the dendritic cells capable of capturing HIV, the researchers studied one family of proteins that are present on the surface of these cells, called Siglecs. It is known that these proteins bind to the gangliosides on the HIV surface. In the laboratory, they mixed the virus with dendritic cells that displayed different quantities of Siglec-1, and found that a higher quantity of Siglec-1 led to those dendritic cells capturing more HIV, which in turn allowed for enhanced transmission of HIV to CD4 T lymphocytes, a process called trans-infection.
The team then tried inhibiting the Siglec-1 protein. They found that the dendritic cells lost their capacity to capture HIV and, importantly, they also lost their ability to transfer HIV to CD4 T lymphocytes. With all these data, the scientists concluded that Siglec-1 is the molecule responsible for HIV entrance into the dendritic cells, and could therefore become a new therapeutic target. "We had the key and now we have found a lock," explains Javier Martínez-Picado. "Now we are already working on the development of a drug that could block this process to improve the efficacy of the current existing treatments against AIDS".