Scientists discover how HIV virus gains access to carrier immune cells to spread infection

A three-dimensional reconstruction of a mature dendritic cell (in gray) where HIV (in red) is stored with the new receptor identified, Siglec-1 (in green). The yellow color appears when the virus (in red) and the receptor (in green) localize within the same compartment of the cell. In blue, the nucleus of the dendritic cell. Credit: Public Library of Science

Scientists from the AIDS Research Institute IrsiCaixa have identified how HIV, the virus that causes AIDS, enters the cells of the immune system enabling it to be dispersed throughout an organism. The new study is published December 18 in the open access journal PLOS Biology.

One of the reasons why we do not yet have a cure for is that the virus infects of the immune system that would normally fight such an infection. The main targets of HIV are named CD4 T lymphocytes (so called because they have the protein CD4 in their membrane), and while more than 20 different drugs are available today to help control HIV, all of them act by blocking the cycle that HIV follows to infect these CD4 T lymphocytes. However, these treatments do not fully act on another cell of the immune system, the dendritic cell, which takes up HIV and spreads it to target CD4 T lymphocytes.

Mature dendritic cells are responsible for activating an by CD4 T lymphocytes, but when they carry viruses, their contact with T lymphocytes causes the virus to be passed on, thus increasing viral spread.

The results continue the research led by ICREA researchers at IrsiCaixa, Javier Martínez-Picado, and Nuria Izquierdo-Useros, in collaboration with research groups from Heidelberg University, Germany, and the University of Lausanne, Switzerland. This team published a previous paper in April 2012, in which they identified , called gangliosides, located on the surface of HIV that are recognized by dendritic cells and are necessary for viral uptake. The new results now identify a molecule on the surface of dendritic cells that recognizes and binds the gangliosides and allows HIV to be taken up by dendritic cells and transmitted to its ultimate target: T lymphocytes.

"We have observed that the protein that acts as a lock for the entrance of HIV could also facilitate the entrance of other viruses," explains Nuria Izquierdo-Useros. "Therefore, our results could also help us understand how other infections might exploit this mechanism of dispersion."

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. Doing so in the laboratory, 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 entrance into the , 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".

More information: Izquierdo-Useros N, Lorizate M, Puertas MC, Rodriguez-Plata MT, Zangger N, et al. (2012) Siglec-1 Is a Novel Dendritic Cell Receptor That Mediates HIV-1 Trans-Infection Through Recognition of Viral Membrane Gangliosides. PLoS Biol 10(12): e1001448. doi:10.1371/journal.pbio.1001448

Related Stories

New memory for HIV patients

Mar 26, 2012

The hallmark loss of helper CD4+ T cells during human immunodeficiency virus (HIV) infection may be a red herring for therapeutics, according to a study published on March 26th in the Journal of Experimental Medicine.

New HIV-vaccine tested on people

Feb 13, 2012

Scientists from the Antwerp Institute of Tropical Medicine, Antwerp University Hospital and Antwerp University have tested a new 'therapeutic vaccine' against HIV on volunteers. The participants were so to say vaccinated ...

Recommended for you

Cambodia orders probe into mass HIV infection

2 hours ago

Cambodian Prime Minister Hun Sen on Thursday ordered a probe into an apparent mass HIV infection believed to have been spread by contaminated needles, as the number of suspected cases passed 100.

A fresh setback for efforts to cure HIV infection

15 hours ago

Researchers are reporting another disappointment for efforts to cure infection with the AIDS virus. Six patients given blood-cell transplants similar to one that cured a man known as "the Berlin patient" have ...

Cambodia village reports mass HIV/AIDS infection

Dec 16, 2014

Cambodian health authorities on Tuesday said more than 80 people—including children and the elderly—who tested positive for HIV/AIDS in a single remote village may have been infected by contaminated needles.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.