|Education||BA, College of Notre Dame|
Despite the ability of highly active antiretroviral therapy (HAART) to suppress viral load in HIV-infected individuals below the limit of detection, it is not able to eliminate infection entirely. Additionally, prolonged use of antiretroviral drugs can lead to drug toxicity and the emergence of drug-resistant viruses, and, due to their cost, these drugs are not widely available in developing countries where infection is rapidly spreading. The ability of HIV to establish latent reservoirs early on in infection leads to the persistence of infection since latent virus is not susceptible to the effects of antiretrovirals. A key unknown regarding HIV latency concerns the location of cellular reservoirs containing latent virus.
HIV infects cells of myeloid lineage, namely macrophages, monocytes and pDCs, and these cells play major roles in the immune response to viral infection. It is thought that macrophages may be an important reservoir of latent virus for many reasons. As a secondary lymphoid organ, the spleen houses an abundant macrophage population that not only plays a role in immune recognition and response, but also in spleen architecture. If splenic macrophages harbor latent virus, then this would make the spleen a significant reservoir of latently infected cells.
In the retrovirus lab, we use an accelerated SIV CNS pigtailed macaque model in combination with a four-drug antiretroviral regimen that produces results that closely mimic HIV infection in humans on HAART. My project entails the characterization of the splenic macrophage population in our model and the evaluation of these cell types as a significant reservoir of latent virus.
Quantitation of gene expression in formaldehyde-fixed and fluorescence-activated sorted cells. Russell JN, Clements JE, Gama L. PLoS One. 2013 Sep 2;8(9):e73849. doi:10.1371/journal.pone.0073849. eCollection 2013. PMID:24023909
Detection of microbial translocation in HIV and SIV infection using the Limulus amebocyte lysate assay is masked by serum and plasma. Balagopal A, Gama L, Franco V, Russell JN, Quinn J, Higgins Y, Smeaton LM, Clements JE, Thomas DL, Gupta A; NWCS 319 and ACTG 5175 study team. PLoS One. 2012;7(8):e41258. Epub 2012 Aug 1. PMID: 22870212
Expansion of a subset of CD14highCD16negCCR2low/neg monocytes functionally similar to myeloid-derived suppressor cells during SIV and HIV infection. Gama L, Shirk EN, Russell JN, Carvalho KI, Li M, Queen SE, Kalil J, Zink MC, Clements JE, Kallas EG. J Leukoc Biol. 2012 May;91(5):803-16. doi: 10.1189/jlb.1111579. Epub 2012 Feb 24. PMID: 22368280