STM: Uncover the mystery of elite controllers: why they are infected with HIV but have nothing to do, and can heal themselves

XIAODONG LIAN AIDS is short for Acquired Immune Deficiency Syndrome, which is caused by HIV infection

However, what is amazing is that there are very few lucky HIV-infected people, accounting for less than 0.

Since the discovery of these rare "elite controllers" for more than a decade, their individual cells have been the focus of research

On December 15, 2021, the Xu Yu team of the Ragon Institute at Harvard University Massachusetts General Hospital (Lian Xiaodong is the first author) published in the journal Science Translational Medicine the title: Signatures of immune selection in intact and defective proviruses distinguish HIV- 1 Research papers of elite controllers

The research team compared the chromosomal integration sites and escape mutations between elite controllers and AIDS patients who need antiretroviral therapy

Collectively, these findings further explain why some people can control their HIV load without the need for treatment

After RNA viruses such as HIV enter the host cell, they first reverse transcribe DNA from RNA (the virus in the form of DNA at this time is called a provirus), and then the proviral DNA integrates with the host cell chromosome to become a part of the host cell genome.

For "elite controllers", after they are infected with the HIV virus, the virus will also integrate into the genome to form a virus reservoir, but the number of proviruses in their cells is significantly lower than the need to receive antiretroviral drugs.

More and more evidences show that the inhibition of HIV virus replication without drug treatment is achieved through effective cellular immune responses, which may induce attenuated virus pools

The research team fully tracked the impact of the antiviral immune response on the complete and defective HIV proviral sequence from the "elite controller", and analyzed the classical escape mutations and HIV-1 chromosomal integration sites as organisms with selective pressure for antiviral immunity Markers

The research team observed that in the "elite controller", defective proviruses are usually integrated in the euchromatin region, while intact proviruses are usually integrated in the heterochromatin region.

Compared with AIDS patients requiring antiretroviral therapy, intact and defective HIV proviruses from "elite controllers" showed a reduced frequency of escape mutations in cytotoxic T cell epitopes and antibody contact areas, which may be due to Because the virus pool in the "elite controller" is small and inducible, it is not enough to drive effective virus immune escape

In addition, about 15% of "elite controllers" have complete HIV proviruses in their bodies with Nef deletions.

These findings reveal the uniqueness of the HIV proviral sequence in the "elite controller" and further explain why some people can control the HIV viral load without the need for treatment

Professor Xu Yu has been committed to research on elite controllers.

This situation has only appeared in the "Berlin patient", a completely cured AIDS patient.

On November 16, 2021, Xu Yu’s team published a paper in the journal Annals of Internal Medicine, reporting the second untreated AIDS patient who was completely cured and referred to it as an “Esperanza patient”
.

Like the San Francisco patient, no complete HIV genome was found in her more than 1.
19 billion blood cells and 500 million tissue cells
.
This indicates that the second untreated, completely self-healing AIDS patient is likely to have appeared
.

Xu Yu said that these findings, especially after the discovery of the second self-healing patient, indicate that there is likely to be a feasible way to help the vast majority of AIDS patients who are unable to heal themselves to achieve a complete cure
.

Original source:

XIAODONG LIAN, et al.
Signatures of immune selection in intact and defective proviruses distinguish HIV-1 elite controllers .
SCIENCE TRANSLATIONAL MEDICINE, 15 Dec 2021, Vol 13, Issue 624.