Researchers from the AIDS Research Institute IrsiCaixa have identified a key piece of the puzzle as to how HIV, the virus that causes AIDS, enters the immune system and spreads throughout an organism, according to a new study published in the open access journal PLOS Biology.

One reason there is no cure for HIV is that the virus infects cells of the immune system that would normally fight such an infection. More than 20 different drugs are available today to help control HIV, and all of them work by blocking the cycle that the virus follows to infect the CD4 T lymphocytes, the main targets of HIV. But these treatments do not fully act on the dendritic cell, another cell of the immune system, which takes up HIV and spreads it to target CD4 T lymphocytes.

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

The Expert Take

ICREA researchers at IrsiCaixa, in collaboration with research groups from Heidelberg University, Germany, and the University of Lausanne, Switzerland conducted previous research in which they identified molecules, called gangliosides, located on the surface of HIV that are recognized by dendritic cells and are necessary for viral uptake.

To further their research, they have now identified 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 the T lymphocytes, their ultimate target.

“We had been looking for the receptor-ligand interaction between HIV-1 and dendritic cells for almost 10 years,” says study author Nuria Izquierdo-Useros. “We knew that this interaction was not the typical protein-protein interaction, so it took a long time to develop the tools and expertise to make the finding. But once we identified the viral ligand earlier in April this year, everything was a little easier and we were able to find its cellular receptor in a record time.”

This basic study has identified a new viral transmission mechanism that could lead to the development of new antiviral drugs, says Izquierdo-Useros.

“Whether this dissemination pathway could be efficiently inhibited to facilitate a future HIV cure is still a long way off from here,” she says. “But we obviously work to understand how to therapeutically translate this new finding and combine it with existing strategies.”

Source and Method

In order to identify the precise molecule located on the membrane of the dendritic cells capable of capturing HIV, the team studied a family of proteins present on these cells, called Siglecs, which bind to the gangliosides on the HIV surface. 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.

They then tried inhibiting the Siglec-1 protein, and found that the dendritic cells lost their capacity to capture HIV, as well as their ability to transfer HIV to CD4 T lymphocytes.

The Takeaway

Thus study marks an important milestone in the understanding of HIV and the search for a cure. Based on these findings, scientists were able to determine that Siglec-1 is the molecule responsible for HIV entrance into the dendritic cells, which could serve as a new target for therapeutic drugs.

According to statistics, more than one million people in the U.S. are living with HIV and one in five people living with HIV are unaware of their infection. Therefore every little bit of information researchers can undercover about this virus is progress and hope for the future.  

Other Research

Countless studies exist that seek to understand the spread of HIV on a molecular basis, while others seek to understand the psychological and social impact of the virus. In a study published in AIDS Care in 2012, researchers measured HIV treatment optimism and its predictors in a sample of young adults in southern Malawi. In 2010, 1,275 women and 470 men between the ages of 16 and 26 were asked about their exposure to people on antiretroviral therapy (ART), sexual risk behavior, HIV status, and beliefs about ART. Among other conclusions, researchers found that overall, respondents reported low levels of HIV treatment optimism and that the relationship between exposure to people on ART and reduced-severity optimism was unclear.

Another study published in AIDS, the official journal of the International AIDS Society, in 2002 sought to understand the association between prevalent or incident herpes simplex virus type 2 (HSV2) infection and the incidence of HIV seroconversion among adults in the general population in rural Tanzania. Based on their results, researchers in this study concluded that HSV2 plays an important role in the transmission of HIV infection in this population, and that effective HSV2 control measures must be identified in order to reduce HIV incidence in Africa.

In a study published in The Lancet in 2011, researchers estimated the contribution of early infection to HIV incidence in Lilongwe, Malawia. They also predicted the future effect of hypothetical prevention interventions targeted at early infection, chronic infection, or both stages. After developing a deterministic mathematical model describing heterosexual HIV transmission, the team concluded that early infection plays an important part in HIV transmission in this sub-Saharan African setting. Their results also suggest that “interventions during chronic infection will probably have incomplete effectiveness unless complemented by strategies targeting individuals with early HIV infection.”