Production of HIV-1 by resting memory T lymphocytes

The persistence of HIV-1 within resting memory CD4 T cells constitutes a major obstacle in the control of HIV-1 infection.

To examine the expression of HIV-1 in resting memory CD4 T cells, using an in-vitro model.

Phytohaemagglutinin-activated peripheral blood mononuclear cells were challenged with T cell-tropic and macrophage-tropic HIV-1 clones, and with a replication-incompetent and non-cytotoxic HIV-1-derived vector (HDV) pseudotyped by the vesicular stomatitis virus glycoprotein G. To obtain resting memory CD4 T cells containing HIV-1 provirus, residual CD25(+), CD69(+) and HLA-DR(+) cells were immunodepleted after a 3 week cultivation period.

In spite of the resting phenotype, the majority of provirus-harbouring T cells expressed HIV-1 genomes and produced infectious virus into cell-free supernatant. The expression of HDV dropped by only 30% during the return of activated HDV-challenged cells into the quiescent phase. Although resting memory T cells generated in vitro expressed HIV-1 and HDV genome when infected during the course of the preceding T cell activation, they were resistant to HIV-1 and HDV challenge de novo. The infected culture of resting memory T cells showed a higher resistance to the cytotoxic effects of HIV-1 in comparison with the same cultures after reactivation by phytohaemagglutinin.

The majority of resting memory T cells infected during the course of a preceding cell activation produces virus persistently, without establishing a true HIV-1 latency. The described system could be used as a model for testing new drugs able to control residual HIV-1 replication in resting memory T cells.