T-Cell Subsets That Harbor Human Immunodeficiency Virus (HIV) In Vivo: Implications for HIV Pathogenesis

Human Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Journal of Virology (Impact Factor: 4.44). 03/2004; 78(3):1160-8. DOI: 10.1128/JVI.78.3.1160-1168.2004
Source: PubMed


Identification of T-cell subsets that are infected in vivo is essential to understanding the pathogenesis of human immunodeficiency virus (HIV) disease; however, this goal has been beset with technical challenges. Here, we used polychromatic flow cytometry to sort multiple T-cell subsets to 99.8% purity, followed by quantitative PCR to quantify HIV gag DNA directly ex vivo. We show that resting memory CD4(+) T cells are the predominantly infected cells but that terminally differentiated memory CD4(+) T cells contain 10-fold fewer copies of HIV DNA. Memory CD8(+) T cells can also be infected upon upregulation of CD4; however, this is infrequent and HIV-specific CD8(+) T cells are not infected preferentially. Naïve CD4(+) T-cell infection is rare and principally confined to those peripheral T cells that have proliferated. Furthermore, the virus is essentially absent from naïve CD8(+) T cells, suggesting that the thymus is not a major source of HIV-infected T cells in the periphery. These data illuminate the underlying mechanisms that distort T-cell homeostasis in HIV infection.

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Available from: Brenna Hill, Apr 10, 2014
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    • "Another example of an advance enabled by cell separation is the isolation of HIV-infected WBCs from patients (Pitcher et al 1999, Douek et al 2002, Brenchley et al 2004) for individual testing; these developments have provided essential insight into the pathology of HIV, leading to better treatment and management of the disease. "
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    • "In HIV-infected persons, the proportion of CMV-Sp cells within CD4 T cells can be higher than healthy controls [20,21]. This maybe because large proportions of CMV-Sp-CD4 T cells are also CD57+ [20,22] and are less likely to be infected by HIV [23]. However, in advanced HIV-infection, CMV-Sp-CD4 T cells are more likely to be absent in those with lower CD4 T cell count, especially with a CD4 T cell count of <50 cells/µL [24,25]. "
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    • "Previous studies using the SIV-macaque model of AIDS have demonstrated that SIV replicates rapidly around the intestine during primary infection, within a couple of weeks post-infection (Veazey et al., 1998; Li et al., 2005; Mattapallil et al., 2005). Moreover, CD4+ T cell depletion upon primary infection with HIV-1 has been reported to occur in the gastrointestinal tract (Meng et al., 2000; Brenchley et al., 2004; Mehandru et al., 2004). However, the dynamic states of the virus during other phases, especially the AIDS stage, have not been defined. "
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