Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo

FR Simonetti, MD Sobolewski, E Fyne… - Proceedings of the …, 2016 - National Acad Sciences
FR Simonetti, MD Sobolewski, E Fyne, W Shao, J Spindler, J Hattori, EM Anderson
Proceedings of the National Academy of Sciences, 2016National Acad Sciences
Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and
make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4+ T
cells. Some of these CD4+ T cells are clonally expanded; most of the proviruses are
defective. It is not known if any of the clonally expanded cells carry replication-competent
proviruses. We report that a highly expanded CD4+ T-cell clone contains an intact provirus.
The highly expanded clone produced infectious virus that was detected as persistent plasma …
Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4+T cells. Some of these CD4+T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4+ T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1–infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4+T cells can be a reservoir of infectious HIV-1.
National Acad Sciences