title: Predicted coreceptor usage at end-stage HIV disease in tissues derived from subjects on antiretroviral therapy with an undetectable plasma viral load.
abstract: HIV cure research is increasingly focused on anatomical tissues as sites for residual HIV replication during combined antiretroviral therapy (cART). Tissue-based HIV could contribute to low-level immune activation and viral rebound over the course of infection and could also influence the development of diseases, such as atherosclerosis, neurological disorders and cancers. cART-treated subjects have a decreased and irregular presence of HIV among tissues, which has resulted in a paucity of actual evidence concerning how or if HIV persists, replicates and evolves in various anatomical sites during therapy. In this study, we pooled 1806 HIV envelope V3 loop sequences from twenty-six tissue types (seventy-one total tissues) of six pre-cART subjects, four subjects with an unknown cART history who died with profound AIDS, and five subjects who died while on cART with an undetectable plasma viral load. A computational approach was used to assess sequences for their ability to utilize specific cellular coreceptors (R5, R5 and X4, or X4). We found that autopsied tissues obtained from virally suppressed cART+ subjects harbored both integrated and expressed viruses with similar coreceptor usage profiles to subjects with no or ineffective cART therapy (i.e., significant plasma viral load at death). The study suggests that tissue microenvironments provide a sanctuary for the continued evolution of HIV despite cART.
authors.affiliation: Bioinfoexperts, LLC, Thibodaux, LA, USA. Electronic address: susanna@bioinfox.com.
authors.forename: S L
authors.initials: SL
authors.lastname: Lamers
authors.affiliation: Natural Selection, Inc., San Diego, CA, USA.
authors.forename: G B
authors.initials: GB
authors.lastname: Fogel
authors.affiliation: Natural Selection, Inc., San Diego, CA, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Liu
authors.affiliation: Bioinfoexperts, LLC, Thibodaux, LA, USA; The University of Florida Emerging Pathogens Institute and the Department of Pathology and Laboratory Medicine, Gainesville, FL, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Nolan
authors.affiliation: The University of Florida Emerging Pathogens Institute and the Department of Pathology and Laboratory Medicine, Gainesville, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Salemi
authors.affiliation: Bioinfoexperts, LLC, Thibodaux, LA, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Barbier
authors.affiliation: Bioinfoexperts, LLC, Thibodaux, LA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Rose
authors.affiliation: The National Neurological AIDS Bank, University of California, Los Angeles, CA, USA; David Geffen School of Medicine and Olive View-UCLA Medical Center, Department of Pathology and Laboratory Medicine, Los Angeles, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Singer
authors.affiliation: The AIDS and Cancer Specimen Resource, San Francisco, CA, USA; The University of California Department of Medicine, San Francisco, CA, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: McGrath
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001344:Autopsy; D060833:Cellular Microenvironment / Q000276:immunology*; D019295:Computational Biology; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000276:immunology; D017423:Sequence Analysis, RNA; D019562:Viral Load / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: Anatomical tissues; Bioinformatics; Combined antiretroviral therapy; Coreceptor; HIV; HIV sequence data