Defining HIV and SIV Reservoirs in Lymphoid Tissues.

Autor: Deleage C; AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Wietgrefe SW; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, MN 55455., Del Prete G; AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Morcock DR; AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Hao XP; Pathology and Histotechnology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Piatak M Jr; AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Bess J; AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Anderson JL; Department of Medicine. Medical School, University of Minnesota, Minneapolis, MN 55455., Perkey KE; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, MN 55455., Reilly C; School of Public Health, Division of Biostatistics, University of Minnesota, Minneapolis, MN 55455., McCune JM; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110., Haase AT; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, MN 55455., Lifson JD; AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Schacker TW; Department of Medicine. Medical School, University of Minnesota, Minneapolis, MN 55455., Estes JD; AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702.
Jazyk: angličtina
Zdroj: Pathogens & immunity [Pathog Immun] 2016 Spring; Vol. 1 (1), pp. 68-106.
DOI: 10.20411/pai.v1i1.100
Abstrakt: A primary obstacle to an HIV-1 cure is long-lived viral reservoirs, which must be eliminated or greatly reduced. Cure strategies have largely focused on monitoring changes in T cell reservoirs in peripheral blood (PB), even though the lymphoid tissues (LT) are primary sites for viral persistence. To track and discriminate viral reservoirs within tissue compartments we developed a specific and sensitive next-generation in situ hybridization approach to detect vRNA, including vRNA+ cells and viral particles ("RNAscope"), vDNA+ cells ("DNAscope") and combined vRNA and vDNA with immunohistochemistry to detect and phenotype active and latently infected cells in the same tissue section. RNAscope is highly sensitive with greater speed of analysis compared to traditional in situ hybridization. The highly sensitive and specific DNAscope detected SIV/HIV vDNA+ cells, including duplexed detection of vDNA and vRNA or immunophenotypic markers in the same section. Analysis of LT samples from macaques prior to and during combination antiretroviral therapy demonstrated that B cell follicles are an important anatomical compartment for both latent and active viral persistence during treatment. These new tools should allow new insights into viral reservoir biology and evaluation of cure strategies.
Databáze: MEDLINE