IrsiCaixa researchers prove that HIV uses a family of immune system cells as a "Trojan horse" to spread out the infection

• Current antiretroviral drugs do not block this HIV route of spread. IrsiCaixa is already investigating, among other strategies to eradicate HIV, a drug against this mechanism that could enhance current clinical treatments
• The study was published in Retrovirology on May 7th

Scientists from IrsiCaixa AIDS Research Institute, jointly promoted by the Obra Social "la Caixa " and the Health Department of the Generalitat de Catalunya, have published a study in Retrovirology journal where they prove for the very first time that myeloid cells (a family of immune system cells) can catch HIV and, instead of initiating an appropriate immune response against it, pass it entirely to his primary target, CD4 T lymphocytes. Using this mechanism, myeloid cells act as "Trojan horses" and help the rapid spread of the virus inside the body.

IrsiCaixa is already looking for a drug against this mechanism, which could enhance current treatments by blocking a different way of spread of the virus. Current antiretroviral treatments difficult infection "virus to cell", but this new line of drugs would block transmission "cell to cell".

HIV entry to the immune system

In 2012, IrsiCaixa researchers discovered how HIV enters the immune system. That study showed that the virus used Siglec-1 molecule to penetrate inside myeloid cells called dendritic cells. Later on, it was demonstrated that HIV uses the same mechanism to enter into other myeloid cells: macrophages and monocytes.

This molecular mechanism was described into in vitro-modified myeloid cells, but it was not known whether Siglec-1 acted in the same way in cells directly isolated from human tissues. Scientists have now worked with not infected people’s tonsils, isolating for the first time myeloid cells directly from human tissue. The results confirm that, also in tissue, these cells can act as a "Trojan horse".

Whenever a pathogen enters our body, myeloid cells play a key role in the activation of the immune response. Its function is to patrol the body, capturing the infectious agents that invade us, isolate their molecules and deliver them to T cells, cells that specifically destroy microbes and already infected cells. However, HIV take refuge inside myeloid cells without actually infecting them, as a way to get to their main targets, CD4 T lymphocytes. Thus, myeloid cells act as “Trojan horses”, as they concentrate the virus in the area of contact with CD4 T cells, favoring their infection, instead of starting an adequate immune response against HIV. This situation creates and ideal scenario for infection of new cells and disease progression.

Key role in the spread of the virus

IrsiCaixa researchers also analyzed tissue from an HIV patient and found that the Siglec-1 receptor was found in these tissues. Thiscorroborates ex vivo what was detected in vitro: that Siglec-1 may play a key role in the spread of the virus within the body.

Therefore, a drug that blocks this way of spread could avoid that HIV use Siglec-1 to enter myeloid cells and use them to infect CD4 T lymphocytes.

Is has also been proved in HIV-infected people that, the more Siglec-1 there are in their cells, the more viral load and the less CD4 T lymphocytes they have. Thus, Siglec-1 could be used as a new biomarker for HIV-infected people.