Research shows HIV spreads by manipulating immune system’s own mechanisms
"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 defense against viral infections and are known to have a beneficial role in the early stages of HIV infection," said Dr. Eric A Cohen, director of the human retrovirology research unit at the IRCM and lead researcher of the study. "The problem is that HIV has developed mechanisms to suppress the Interferon response and, until now, little was known about how this was achieved."
Vpu, a viral protein in HIV, deceives the immune system with its own regulatory process, which allows the virus to avoid the immune system’s first defense line.
"When pDCs encounter HIV-infected cells, the production of Interferon is regulated by a protein on the infected cell's surface called BST2," said Dr. Mariana Bego, first author of the study and a research associate in Cohen's lab. "BST2 has the ability to bind to and activate a receptor called ILT7, found on the surface of pDCs, which in turn, sends a signal that suppresses the production of Interferon and halts its defensive functions. 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. 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."
Cohen also leads CanCURE, a team of leading Canadian researchers working toward an HIV cure.
"The hope for a definitive cure and an effective vaccine has been frustrated by HIV's endless propensity to subvert the host's defenses and persist in small populations of long-lasting reservoirs despite antiretroviral therapy," Cohen said. "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 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."
Further details are available in PLOS Pathogens, a scientific journal.