Unique elite controller HIV reservoir

Xu Yu, MD, the leader of the Ragon group, recently published a study entitled “Definite viral reservoirs in individuals with spontaneous control of HIV-1.” Nature.. Yu’s lab, in collaboration with Lagon’s group leaders Matthias Richterfeld (Doctor of Medicine) and Mary Carrington (Doctor of Medicine), arrayed billions of cells from 64 elite controllers (people living with HIV). It was decided that 41 people would naturally suppress the virus without the need for drug therapy, and antiretroviral drugs (ART). Unlike individuals treated with ART, the elite controller’s viral reservoir does not appear to be reactivating. This probably helps the elite controller maintain voluntary, drug-free control of HIV and may represent a salient feature of a functional cure for HIV infection.

HIV affects more than 35 million people worldwide and can be effectively controlled with ART’s daily regimen, but it cannot be cured. Upon infection, a retrovirus such as HIV places a copy of the viral genetic material in the cell’s genome, creating a reservoir of the virus, a sanctuary for HIV throughout the body despite ART. A complete copy of the virus, or an intact virus genome, Integrated into the cell’s genome, can be used to make new copies of HIV. For people living with HIV, this means that when they stop taking ART, the intact viral genome, previously integrated into the cell’s genome, begins to make new copies of the virus, resulting in rapid viral rebound. Disease progression.. HIV virus reservoirs represent a major obstacle to HIV treatment.

Elite controller immune system mediated by T cells Immune reaction Control the virus without drugs, until the virus is completely undetectable in standard assays. Understanding the interaction of HIV with their immune system is key to helping people living with HIV suppress the virus without routine treatment and achieve what is known as a functional cure. maybe.

Yu’s group is Elite controllerAccurately map the location of the intact HIV genome within the human genome using next-generation sequencing technology. With an elite controller, they discovered that HIV was found in a genomic location that researchers often call the genetic desert. In these inactive parts of the human genome, human DNA does not turn on and is unable to effectively express HIV, but remains in a “blocked and locked” state. This means that HIV is not able to cause disease because it is confined to the cell’s genome and the viral genome is blocked from being used to make the virus.

“This position of the viral genome in the elite controller, like most people living with HIV-1, is very unusual, with HIV located in an active human gene where the virus is easily produced. “

When the authors collected cells from the elite controller and infected them with HIV in the lab, they found that the virus Active site Inactive genes Not in the desert, but in the cell genome. This suggests that the unique viral reservoir of the elite controller may be the result of an HIV-suppressed T cell response that removes the entire viral genome from active sites.

Which virus reservoir the researchers Virus Helps target treatment for active or rebound competent reservoirs after treatment has stopped. This study suggests that the ability to activate the types of T cell immunity present in the elite controller could potentially eliminate rebound competent virus reservoirs in HIV-infected individuals and achieve functional therapies. .. Viral DNA in the inactive part of Human genome, May be allowed to exist without causing illness.

Yu’s group made another discovery. elite Controller participants were unable to find intact HIV in more than 1.5 billion cells analyzed. This raises the possibility of a “bactericidal treatment” for HIV. Immune system We’ve removed all of the intact HIV genome from the body, but on rare occasions it can be accomplished spontaneously.