Researchers may have found the answer to the question as to how the HIV virus persists in the body, and replication resumes if treatment is interrupted.
They recently discovered T memory stem cells, which could be long-term viral reservoir, and may be potential targets for future treatment of HIV.
Corresponding author Mathias Lichterfeld, MD, of the MGH Infectious Disease Division, said that most human cells are short lived, so it has been unclear how HIV manages to stick around for decades in spite of very effective antiviral treatment.
Lichterfeld said that this question led to the hypothesis that HIV might infect stem cells - the most long-lasting cells in the body - but traditional organ-specific stem cells, even those that give rise to all immune and blood cells, are resistant to HIV infection, asserting that they 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.
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.
The study is set to be published online in the journal Nature Medicine.
