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Latent HIV infection allows virus to persist in HIV-infected individuals in spite of antiretroviral therapy. In addition to the well-studied reservoir of latent virus in resting memory CD4+ T cells, we have recently proposed that hematopoietic progenitor cells (HPCs) in the bone marrow serve as a reservoir for latent HIV. Here, I first investigate whether HIV envelope tropism impacts the ability of the virus to infect different types of HPCs. I find that HIV envelopes that are able to use CXCR4 as a co-receptor permit infection of immature, multipotent HPCs defined by expression of the cell surface marker CD133, whereas CCR5-tropic HIV has a greatly reduced capacity to infect these cells. Furthermore, I find that a CXCR4-tropic HIV envelope can infect hematopoietic stem cells that support long-term, multilineage engraftment in mice. As hematopoietic stem cells can live for the entire lifespan of a person, latent HIV infection of these cells could create a very long-lived reservoir of virus. I next examine the cellular factors that promote latency in HPCs and find that HIV can establish a latent infection in multiple HPC subsets, including immature HPCs. Latent infection in these cells can be reversed by activation of the transcription factor NF-kappaB as well as by inhibition of histone deacetylases. Finally, I investigate whether the CD133+ subset of HPCs harbors HIV genomes in HAART-treated patients with undetectable viral loads. I detect HIV genomes in CD133-sorted cell populations in 6 of 11 donors, including two donors who have had undetectable viral loads for more than 8 years. Furthermore, for at least 5 of these 6 donors I demonstrate that CD3+ T cells are present at extremely low levels in the CD133-sorted populations and are therefore unlikely to contribute to the HIV DNA detected in these samples. Together, these findings illuminate the potential of long-lived, CD133+ HPCs to serve as a reservoir for latent virus in HIV-infected individuals. Further study of how latent infection in HPCs and T cells can be reversed to eliminate these viral reservoirs may lead us closer to a cure for HIV.

The goal of this investigation was to evaluate treatment outcomes associated with tuberculosis in a correctional environment. We also conducted a case-control study to determine if social history variables such as tobacco use, alcohol use, intravenous drug abuse, and non-intravenous drug abuse were significant risk factors for tuberculosis infection.Data on cases (individuals with positive tuberculin skin tests (TSTs)) and age-matched controls (individuals with negative TSTs) were extracted from medical charts at an Ohio Department of Rehabilitation and Correction (ODRC) facility in Orient, Ohio. Eighty-nine cases were identified and age-matched controls were randomly chosen for 88 individuals. All 89 of the cases identified at the facility received a diagnosis of latent tuberculosis infection (LTBI), and 75 (84%) of the inmates had either completed or were receiving treatment for LTBI. Comparisons between the cases and controls revealed significantly higher rates of asthma (p=0.03) and rheumatoid arthritis (pOverall treatment outcomes from the study were encouraging with a majority of the infected inmates receiving and completing treatment for LTBI. No significant predictors of infection were found but more detailed information on frequency and duration of substance abuse in future studies could prove otherwise. Some concerns were noted with regards to a lack of documentation of HIV results and treatments, however the facility demonstrates the ability of a correctional institution to detect and treat LTBI among a highly vulnerable and disadvantaged population.

Latent feline leukemia virus (FeLV) infections, in which proviral DNA is integrated into host DNA, but not actively transcribed, are suspected to be associated with many diseases. Bone marrow is the suspected site of the majority of latent infections. The purpose of this study was to determine if polymerase chain reaction (PCR) could detect FeLV proviral DNA in bone marrow and provide a method of detecting latent infections. Blood and bone marrow samples from fifty cats and bone marrow from one fetus were collected; sixteen had FeLV-associated diseases. Serum ELISA, blood and bone marrow immunofluorescent antibody test (IFA), and blood and bone marrow PCR were performed on each cat, and IFA and PCR on bone marrow of the fetus. Forty-one cats were FeLV negative. Five cats and one fetus were persistently infected with FeLV. Four cats were discordant; two ELISA positive with other tests negative, one bone marrow IFA negative with other tests positive, and one bone marrow IFA positive with other tests negative. No cats were positive on bone marrow PCR only. These results indicate that PCR can detect FeLV in bone marrow, but no cats in this study harbored FeLV only in the bone marrow. Not all cats with FeLV-associated diseases are persistently or latently infected with FeLV.