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Quantitative Imaging Analysis of the Spatial Relationship between Antiretrovirals, Reverse Transcriptase Simian-Human Immunodeficiency Virus RNA, and Collagen in the Mesenteric Lymph Nodes of Nonhuman Primates.
Scholz, Erin M B; Mwangi, Joseph N; De la Cruz, Gabriela; Nekorchuk, Michael; Chan, Chi Ngai; Busman-Sahay, Kathleen; Adamson, Lourdes; Luciw, Paul; Fedoriw, Yuri; Estes, Jacob D; Rosen, Elias P; Kashuba, Angela D M.
Afiliación
  • Scholz EMB; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Mwangi JN; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • De la Cruz G; School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Nekorchuk M; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
  • Chan CN; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
  • Busman-Sahay K; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
  • Adamson L; School of Medicine, University of California at Davis, Davis, California, USA.
  • Luciw P; School of Medicine, University of California at Davis, Davis, California, USA.
  • Fedoriw Y; School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Estes JD; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
  • Rosen EP; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Kashuba ADM; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA akashuba@unc.edu.
Antimicrob Agents Chemother ; 65(6)2021 05 18.
Article en En | MEDLINE | ID: mdl-33782003
Human immunodeficiency virus (HIV) persistence in tissue reservoirs is a major barrier to HIV cure. While antiretrovirals (ARVs) suppress viral replication, antiretroviral therapy (ART) interruption results in rapid rebound viremia that may originate from lymphoid tissues. To understand the relationship between anatomic distribution of ARV exposure and viral expression in lymph nodes, we performed mass spectrometry imaging (MSI) of 6 ARVs, RNAscope in situ hybridization for viral RNA (vRNA), and immunohistochemistry of collagen in mesenteric lymph nodes from 8 uninfected and 10 reverse transcriptase simian/human immunodeficiency virus (RT-SHIV)-infected rhesus macaques dosed to steady state with combination ART. MATLAB-based quantitative imaging analysis was used to evaluate spatial and pharmacological relationships between these ARVs, viral RNA (both vRNA+ cells and follicular dendritic cell [FDC]-bound virions), and collagen deposition. Using MSI, 31% of mesenteric lymph node tissue area was found to be not covered by any ARV. Additionally, 28% of FDC-trapped virions and 21% of infected cells were not exposed to any detected ARV. Of the 69% of tissue area that was covered by cumulative ART exposure, nearly 100% of concentrations were greater than in vitro 50% inhibitory concentration (IC50) values; however, 52% of total tissue coverage was from only one ARV, primarily maraviroc. Collagen covered ∼35% of tissue area but did not influence ARV distribution heterogeneity. Our findings are consistent with our hypothesis that ARV distribution, in addition to total-tissue drug concentration, must be considered when evaluating viral persistence in lymph nodes and other reservoir tissues.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / Síndrome de Inmunodeficiencia Adquirida del Simio / Virus de la Inmunodeficiencia de los Simios Límite: Animals Idioma: En Revista: Antimicrob Agents Chemother Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / Síndrome de Inmunodeficiencia Adquirida del Simio / Virus de la Inmunodeficiencia de los Simios Límite: Animals Idioma: En Revista: Antimicrob Agents Chemother Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos