The extent to which HIV may infect CD34+ hematopoietic progenitor cells (stem cells) in the bone marrow has been the subject of controversy for more than two decades. Early studies documented the presence of HIV in CD34+ cells in a subset of people with advanced disease, but a subsequent report offered little evidence of infection in asymptomatic individuals. In the new issue of Nature Medicine, a group of researchers from the University of Michigan revisit the issue in a paper that garnered substantial press coverage when it was released online a few weeks ago. The paper contains data indicating that CD34+ stem cells can be infected in vitro and also reports that HIV DNA could be detected in CD34+ cells sampled from the bone marrow of people with HIV infection, including four out of nine individuals on antiretroviral therapy (ART) with undetectable viral loads in peripheral blood. The researchers conclude that stem cells may be an important reservoir of latent HIV in people on ART.
There are some caveats, however, and it will be important for the findings to be confirmed (the researchers themselves acknowledge as much, stating: “further studies are needed to show that CD34+ stem cells are infected”). The in vitro work is primarily based on HIV isolates that are dual-tropic or target the X4 co-receptor, and the efficiency of infection by CCR5-using HIV appears lower (see the supplemental information panel “a” and compare the percentage of infected cells with the X4 and dual tropic viruses NL4-3 and 89.6 to the R5 viruses 94UG, MJ4 and YU2). The numbers of individuals sampled for the in vivo results is also very small and analyses of larger cohorts are needed.
Nat Med. 2010 Mar 7. [Epub ahead of print]
Carter CC, Onafuwa-Nuga A, McNamara LA, Riddell J 4th, Bixby D, Savona MR, Collins KL.
 Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA.  Medical Scientist Training Program, University of Michigan, Ann Arbor, Michigan, USA.  These authors contributed equally to this work.
HIV causes a chronic infection characterized by depletion of CD4(+) T lymphocytes and the development of opportunistic infections. Despite drugs that inhibit viral spread, HIV infection has been difficult to cure because of uncharacterized reservoirs of infected cells that are resistant to highly active antiretroviral therapy (HAART) and the immune response. Here we used CD34(+) cells from infected people as well as in vitro studies of wild-type HIV to show infection and killing of CD34(+) multipotent hematopoietic progenitor cells (HPCs). In some HPCs, we detected latent infection that stably persisted in cell culture until viral gene expression was activated by differentiation factors. A unique reporter HIV that directly detects latently infected cells in vitro confirmed the presence of distinct populations of active and latently infected HPCs. These findings have major implications for understanding HIV bone marrow pathology and the mechanisms by which HIV causes persistent infection.