Study identifies population of stem-like cells where HIV persists in spite of treatment

“We have discovered that a new group of T cells, called T memory stem cells, are susceptible to HIV and likely represent the longest lasting cellular niche for the virus,” Mathias Lichterfeld, an assistant professor at Harvard Medical School and corresponding author of the report. Credit: File photo by Thomas Earle

Although antiviral therapy against HIV suppresses viral replication and allows infected individuals to live relatively healthy lives for many years, the virus persists in the body, and replication resumes if treatment is interrupted. Now investigators from Massachusetts General Hospital (MGH) and the Ragon Institute of MGH, MIT and Harvard may have found where the virus hides - in a small group of recently identified T cells with stem-cell-like properties.

"Most are short lived, so it has been unclear how HIV manages to stick around for decades in spite of very effective ," says Mathias Lichterfeld, MD, of the MGH Infectious Disease Division, corresponding author of the report receiving advance online publication in Nature Medicine. "This question led to the hypothesis that HIV might infect - the most long-lasting cells in the body - but traditional organ-specific stem cells, even those that give rise to all immune and , are resistant to HIV infection. We have discovered that a new group of T cells, called T memory stem cells, are susceptible to HIV and likely represent the longest lasting cellular niche for the virus."

HIV has such a devastating impact on the human immune system because it infects the CD4-positive T cells that normally direct and support the infection-fighting activities of other . Several subtypes of CD4 T cells have different functions; and all are capable of being infected by HIV, although antiviral treatment keeps the virus in those cells from replicating. Most of these CD4 T cells are short-lived and die relatively soon. What is distinct about CD4 T memory stem cells is their ability to live for decades, while giving rise to several subgroups of T cells. Therefore, HIV-infected T memory stem cells could continuously regenerate new HIV-infected cells, fueling the fire of HIV persistence in the human body.

The MGH/Ragon team found that T memory stem cells express both CD4 and CCR5 - the receptor proteins used by HIV to enter cells - suggesting that these long-lived cells could be the long-sought HIV reservoir. They then found that these cells can be readily infected with HIV, which was unexpected since traditional stem cells resist HIV infection. Importantly, the investigators found that levels of HIV DNA in patients receiving long-term antiviral treatment were highest in T memory stem cells.

Testing blood samples that had been taken from patients soon after initial infection and several years later revealed that the viral sequences found in T memory stem cells after 6 to 10 years of treatment were similar to those found in circulating T cells soon after infection, indicating that HIV had persisted relatively unchanged in T memory stem cells. In addition, the amount of HIV DNA in these cells remained relatively stable over time, even after long-term treatment caused viral levels to drop in other T cell subsets.

"Our findings suggest that novel, specific interventions will have to be designed to target HIV-infected T memory stem cells," says Lichterfeld, an assistant professor of Medicine at Harvard Medical School. "Methods of inhibiting stem cell pathways are being studied to eliminate cancer stem cells - persistent cells that are responsible for tumor recurrence after conventional treatments kill proliferating tumor cells. We are now investigating whether any of the drugs that target might be effective against HIV-infected T memory stem cells.

"Identifying the reservoirs for HIV persistence is a critical step toward developing interventions that could induce a long-term remission without the need for antiviral medication, or possibly eliminate the virus entirely," Lichterfeld adds. "Although a real cure for HIV has been elusive, it is not impossible."

More information: HIV-1 persistence in CD4+ T cells with stem cell–like properties, DOI: 10.1038/nm.3445

Related Stories

New target to fight HIV infection identified

Oct 01, 2013

A mutant of an immune cell protein called ADAP (adhesion and degranulation-promoting adaptor protein) is able to block infection by HIV-1 (human immunodeficiency virus 1), new University of Cambridge research reveals. The ...

Scientists discover how HIV kills immune cells

Jun 05, 2013

Untreated HIV infection destroys a person's immune system by killing infection-fighting cells, but precisely when and how HIV wreaks this destruction has been a mystery until now. New research by scientists at the National ...

New memory for HIV patients

Mar 26, 2012

The hallmark loss of helper CD4+ T cells during human immunodeficiency virus (HIV) infection may be a red herring for therapeutics, according to a study published on March 26th in the Journal of Experimental Medicine.

Recommended for you

New study reveals why some people may be immune to HIV-1

Nov 20, 2014

Doctors have long been mystified as to why HIV-1 rapidly sickens some individuals, while in others the virus has difficulties gaining a foothold. Now, a study of genetic variation in HIV-1 and in the cells ...

Virus discovery could impact HIV drug research

Nov 20, 2014

A research team led by Portland State University (PSU) biology professor Ken Stedman has unlocked the structure of an unusual virus that lives in volcanic hot springs. The discovery could pave the way for better drugs to ...

User comments

Adjust slider to filter visible comments by rank

Display comments: newest first

DanPoynter
not rated yet Jan 13, 2014
More Information: New Book on Stem Cell Transplants.

TRANSPLANT HANDBOOK FOR PATIENTS: Replacing #Stem Cells in Your Bone #Marrow.
By a 75-year old author, in Day +164 since his transplant, who is setting records for recovery.
This book helps the #cancer patient, caregiver, and family to understand the #stem cell #transplant journey.
http://TransplantHandbook.com

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.