Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2013

HIV infection of Hematopoietic Progenitor Cells  (#32)

Adewunmi Nuga 1 , Lucy McNamara 1 , Nadia Sebastian 1 , Chris Carter 1 , Dale Bixby 1 , James Riddell 1 , Michael Savona 1 , Mark Shackleton , Sean Morrison 1 , Kathleen Collins 1
  1. University of Michigan, Ann Arbor, MI, United States

HIV infection is characterized by gradual immune system collapse, hematopoietic dysfunction and the establishment of long term cellular reservoirs. We have found that HIV enters multipotent hematopoietic progenitor cells and establishes active and latent infections1 . Latent infection of HPC can be reactivated by myeloid differentiation1 .  In addition, we have found that HIV can infect multipotent progenitors including long-lived hematopoietic stem cells (HSCs) that have the potential to establish viral reservoirs that persist for the life of the infected person.  Specifically, we found that cells targeted by HIV have all the characteristics of hematopoietic stem cells in that they can stably engraft and generate multiple hematopoietic lineages in a xenograft model2 . Furthermore, we found that the capacity to use the chemokine receptor CXCR4 for entry determines whether a virus will enter multipotent versus differentiated progenitor cells2 . Finally, we demonstrate that HIV genomes can be detected in CD133+ HPCs from a subset of donors with long term viral suppression3 . Because HSCs live for the life span of the infected person and are crucial for hematopoietic health, these data may explain the poor prognosis associated with CXCR4-tropic HIV infection and suggest HSC as long-lived cellular reservoirs of latent HIV.  Strategies that reactive HIV gene expression in HSCs without causing differentiation may help clear these reservoirs4 .

  1. Carter, C.C., Onafuwa-Nuga, A., Riddell, J., Bixby, D., Savona, M.R. and Collins, K.L., (2010) HIV-1 Infects Multipotent Progenitor Cells Causing Cell Death and Establishing Latent Cellular Reservoirs, Nature Medicine, Apr;16(4):446-51. Epub 2010 Mar 7, PubMed PMID: 20208541
  2. Carter, C.C., McNamara, L.A., Onafuwa-Nuga, A., Shackleton, M., Riddell, J., Bixby, D., Morrison, S.J., and Collins, K.L., (2011) HIV-1 utilizes the CXCR4 chemokine receptor to infect multi-potent hematopoietic stem cells, Cell Host & Microbe, Mar 17;9(3):223-34
  3. McNamara, L.A., Onafuwa-Nuga, A., Sebastian, N., Riddell, J, Bixby, D., and Collins, K.L., (2013) CD133+ HPCs harbor HIV genomes in a subset of optimally treated people with long-term viral suppression
  4. McNamara LA, Ganesh JA, Collins KL. Latent HIV-1 infection occurs in multiple subsets of hematopoietic progenitor cells and is reversed by NF-kappaB activation. J Virol. 2012 Sep;86(17):9337-50. doi: 10.1128/JVI.00895-12. Epub 2012 Jun 20. PubMed PMID: 22718820; PubMed Central PMCID: PMC3416176.