HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immunodeficiency syndrome).
HIV is largely divided into type 1 and type 2, and ‘group M’, a subtype of type 1, is considered the main culprit behind the AIDS epidemic.
HIV-1 has an excellent ability to evade the human immune system.
However, the human innate immune system catches HIV-1 invasion early.
Scientists at the Scripps Institute in the United States have uncovered how the human innate immune system can do this.
The innate immune system identified the capsid enclosing the HIV-1 particle in two stages and took action.
This was similar to repeatedly checking the identity of an Internet user with a password and e-mail.
This finding could be an important insight that opens up new avenues for the development of treatments and vaccines for HIV infection.
It will also help us understand how the innate immune system is involved in neurodegenerative and autoimmune diseases such as Alzheimer’s.
The results of this research conducted by Professor Sumit Chanda of the Department of Immunology and Microbiology at the Scripps Research Institute were published in the journal Molecular Cell on the 8th (local time) in the journal Molecular Cell.
The innate immune system is activated prior to the acquired adaptive immune system.
While the innate immune system is the first line of defense against invading foreign pathogens, the adaptive immune system is the second line of defense.
The adaptive immune system involves more specialized immune components, such as the production of antibodies.
One of the important tasks of the innate immune system is to identify foes.
It refers to the distinction between self-protein or genetic material and pathogens such as viruses introduced from the outside.
A key role in this case is a protein called cGAS (circulating GMP-AMP synthetase) of the innate immune system.
cGAS detects the presence of foreign invaders by capturing DNA floating in the cell.
When this protein detects the intruder’s DNA, the molecular pathways that fight them are also activated.
However, since HIV-1 is an RNA virus, it produces very little DNA that cGAS can identify.
This is why we don’t understand how the innate immune system detects the invasion of HIV-1.
Professor Chanda’s team confirmed the double ‘security check’ system of the innate immune system.
When HIV-1 entered the cell, it first released PQBP1 (polyglutamine binding protein 1), which then detected the virus’s capsid.
This initial identification was made before the virus multiplied.
Soon after, the viral capsid was covered with PQBP1, which served as a warning signal to call cGAS.
Then, when the PQBP1-covered viral envelope began to disintegrate, cGAS further activated the immune response pathway.
It was a surprising finding that HIV-1 activates the innate immune system in a two-step process when infected.
It was similar to entering a password when using the Internet and verifying the identity again by e-mail.
Other viruses that code for DNA do not go through a double-check when they activate cGAS in the innate immune system.
The ‘double confirmation’ mechanism of the innate immune system could be a useful insight for developing new vaccine development strategies.
This is so in the sense that HIV-1, which invades cells, can take advantage of a chain immune response that is initiated before it begins to multiply, that is, immediately after the viral capsid is coated with the PQBP1 protein.
The results of this study also shed new light on how our body responds to autoimmune diseases and neurodegenerative inflammatory diseases.
For example, the PQBP1 protein was found to stimulate the inflammatory cGAS pathway by interacting with the tau protein that causes Alzheimer’s disease.
The research team plans to continue studying how the innate immune system is involved in the development and progression of Alzheimer’s disease and other diseases, and how it distinguishes between own cells and foreign cells.
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