HIV

They have discovered an HIV protein known as Vpu which tricks the immune system using its own regulatory process to evade the host’s defenses. This opens up new possibilities for finding a cure for HIV and its prevention.

 

The study was trying to discover how HIV manages to compromise antiviral responses in the acute infection stage which is when the virus gets established in the body. This stage is considered critical in determining the complexity, progression and extent of the disease. This is when establishes infections in lon-lasting cellular reservoirs. They harbor the virus and hide it from antiviral drugs and the immune system.

 

"An important component in this process is a group of proteins collectively called type 1 Interferons, which are the immune system's first line of defence against viral infections and are known to have a beneficial role in the early stages of HIV infection," said Dr. Cohen, Director of the Human Retrovirology research unit at the IRCM. "The problem is that HIV has developed mechanisms to suppress the Interferon response and, until now, little was known about how this was achieved."

 

The interferon is mainly produced by a small population of immune cells (pDCs) which are responsible for providing immediate infection defenses. The detect invaders in the body and secrete Interfereon when they find a pathogen. This then triggers various defense mechanisms in cells that are close by which should lead to the prevention of the expansion and dissemination of the virus.

 

"When pDCs encounter HIV-infected cells, the production of Interferon is regulated by a protein located on the infected cell's surface called BST2," Mariana Bego, PhD, explained. "BST2 has the ability to bind to and activate a receptor called ILT7, found on the surface of pDCs, which, in turns, sends a signal that suppresses the production of Interferon and halts its defensive functions. Interestingly, BST2 is also responsible for restricting HIV production by trapping the virus at the cell surface before it can exit infected cells and disseminate. However, HIV uses the viral protein Vpu to counteract BST2 antiviral activity."

 

"With this study, we uncovered a unique mechanism whereby HIV exploits the regulatory process between BST2 and ILT7 to limit the body's antiviral response, which allows the virus to spread and leads to persistent infection," Dr. Bego addded. "We found that HIV, through Vpu, takes advantage of the role played by BST2 by maintaining its ability to activate ILT7 and limit the production of Interferon, all the while counteracting its direct antiviral activity on HIV production."

 

"The hope for a definitive cure and an effective vaccine has been frustrated by HIV's endless propensity to subvert the host's defences and persist in small populations of long-lasting reservoirs despite antiretroviral therapy," Dr. Cohen described, leader of a  team of leading Canadian researchers CanCURE,  who are working towards a cure for HIV. "Our findings can provide tools to enhance antiviral responses during the early stages of infection. By blocking Vpu's action, we could prevent early viral expansion and dissemination, while also allowing pDCs to trigger effective antiviral responses. We believe that such interventions during primary infection have the potential to limit the establishment and complexity of viral reservoirs, a condition that seems required to achieve a sustained HIV remission."

 

 

"The discovery by Drs. Bego and Cohen, which explains how the virus can't be held down or wiped out during early periods of infection, will bring us closer to ending HIV/AIDS," said a member of CanCURE Community Liaison. "By filling an important gap in knowledge, this new study will advance research for an HIV cure."