Nature: Uncover the characteristics of the special HIV library in the body of the HIV elite controller!

September 4, 2020 // -- In a recent study published in the international journal Nature, scientists from Massachusetts General Hospital and other institutions successfully sequenced hundreds of millions of cells in 64 HIV elite controllers and 41 individuals taking antiretroviral drugs (ART). Elite controllers, i.e. the body can successfully suppress HIV levels and disease progression without medication, and unlike individuals treated with ART, the HIV library in elite controllers does not appear to be activated, which may help them maintain control of spontaneous and drug-free HIV levels, while also revealing a significant feature of functional cures for HIV infection.
Photo Source: NIAID HIV affects the health of more than 35 million people worldwide, and these patients effectively control the virus through daily ART therapy, but they cannot be cured, and once infected, retrovirus such as HIV put their genetic material into the genome of host cells, creating a potential library of viruses, meaning that despite ART treatment, H persists in the body IV, when a complete copy of the virus or genome is inserted into the genome of the host cell, the virus uses the host cell to make a new copy of HIV, which means that if ART therapy is stopped, the complete virus genome previously integrated into the host cell genome will begin to make new copies of the virus, leading to rapid virus rebound and disease progression, and now the HIV library remains the main obstacle and problem in the treatment of HIV.
Elite Controller's body's immune system uses T-cell-mediated immune responses to control the virus without taking the drug, thus using standard testing to completely detect the virus in these populations, and reveals the interaction between the elite controller's body's immune system and HIV, or helps HIV-infected people use their immune systems to suppress viral progress without taking daily medication.
researcher Yu pointed out that in this study, we studied the HIV library in the operator's controller, using a new generation of sequencing technology to accurately map the exact location of the complete HIV genome in the human genome, the researchers found that in elite controllers, HIV often appears in what researchers call the genome of the gene desert unknown, In the inactive parts of the human genome, human DNA may never be turned on, and HIV is not effectively expressed, and it is in a closed and locked state, which means that HIV is locked into the cell genome, and the virus genome is blocked to create more viruses, so it cannot cause disease.
Elite Controller virus genomes may be highly atypical, as researchers have observed in the vast majority of people infected with HIV-1, HIV tends to be located at active human gene locations where the virus can easily produce; When infected cells, they found that the virus was able to integrate into the active bits of the cell genome, not the inactive gene desert regions, suggesting that the elite controller's special library of viruses may be the result of the elimination of the entire viral genome from the active bits by the cellular immune response that inhibits HIV.
If scientists can identify which virus libraries will make new copies of the virus after patient therapy stops, then it may be possible to help develop new targeted therapies to target HIV libraries with active or potentially rebounding properties, and if researchers can activate certain types of T-cell immunity present in elite controllers, they may be able to completely eliminate the viral library that bounces in HIV-infected people and ultimately achieve a functional cure for HIV.
that remains in the inactive region of the human genome may continue to exist without causing disease.
The researchers concluded that their analysis of one of the elite controllers found no complete HIV virus in the 1.5 billion cells analyzed may raise the possibility of a new treatment where the participant's body's immune system can remove all complete HIV genomes from their bodies, which may be possible in extremely rare cases.
() Original source: Jiang, C., Lian, X., Gao, C. et al. Distinct viral reservoirs in individuals with spontaneous control of HIV-1. Nature (2020). doi:10.1038/s41586-020-2651-8.