Human immunodeficiency virus 1, more commonly known as HIV-1, is known for its uncanny ability to evade the immune system. Scientists at Scripps Research and collaborators have now revealed how our innate immune system, the body’s first line of quick defense in attacking foreign invaders, detects HIV-1, even in small concentrations, in a new study.
The study, published in the peer-reviewed journal Molecular Cell, reveals the two-step molecular strategy that activates the innate immune response when exposed to HIV-1.
This discovery could impact drug development for HIV treatments and vaccines, as well as shape our understanding of how the innate immune response is implicated in other areas, including neurodegenerative disorders such as Alzheimer’s.
“This research delineates how the immune system can recognize a very cryptic virus, and then activate the downstream cascade that leads to immunological activation,” says Sumit Chanda, Ph.D., professor in the Department of Immunology and Microbiology.
“This research delineates how the immune system can recognize a very cryptic virus, and then activate the downstream cascade that leads to immunological activation.”Sumit Chanda, Ph.D.
“From a therapeutic potential perspective, these findings open up new avenues for vaccines and adjuvants that mimic the immune response and offer additional solutions for preventing HIV infection,” Dr. Chanda added.
The researchers were initially surprised to find that two steps are required for innate immune activation against HIV-1, as most other DNA-encoding viruses only activate cGAS in one step. This is a similar concept to technologies that use two-step authentication, such as requiring users to enter a password and then respond to a confirmation email.
This two-part mechanism also allows the expansion of vaccination approaches that can exploit the immune cascade that is initiated before the virus can start to replicate in the host cell after PQBP1 has decorated the molecule.
“While the adaptive immune system has been the main focus for HIV research and vaccine development, our discoveries clearly show the critical role the innate immune response plays in detecting the virus,” says Sunnie Yoh, Ph.D., first author of the study and senior staff scientist in Chanda’s lab.
“In modulating the narrow window in this two-step process – after PQBP1 has decorated the viral capsid, and before the virus is able to insert itself into the host genome and replicate – there is the potential to develop novel adjuvanted vaccine strategies against HIV-1,” Dr. Yoh added.