Eleni Giatsou1, Basma Abdi1, Isabelle Plu2, Nathalie Desire1, Romain Palich3, Vincent Calvez1, Danielle Seilhean2, Anne-Geneviève Marcelin1, Aude Jary1. 1. Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié Salpêtrière, Laboratoire de Virologie. 2. Sorbonne Université, APHP, Hôpital Pitié Salpêtrière, Département de Neuropathologie Raymond Escourolle. 3. Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié Salpêtrière, Service de Maladies Infectieuses et Tropicales, Paris, France.
Abstract
OBJECTIVES: To examine viral diversity and resistance mutations in different brain areas in cases of HIV-encephalopathy. DESIGN: Twelve postmortem brain areas from three cases of possible or certain HIV-encephalopathy were analyzed. METHODS: After amplification of the reverse transcriptase and the V3 loop region of the gp120 protein, ultradeep sequencing was performed with Illumina technology. Phylogenetic analysis was performed with Fastree v2.1 using the generalized time-reversible (GTR) model. Identification of resistant viral variants was performed on Geneious software, according to HIV-1 genotypic drug resistance interpretation's algorithms, 2018 administered by the French Agency for Research on AIDS and Viral Hepatitis. RESULTS: Phylogenetic analysis revealed significant inter-regional and intra-regional diversity reflecting persistent HIV-1 viral replication in the different brain areas. Although some cerebral regions shared HIV-variants, most of them harbored a specific HIV-subpopulation reflecting HIV compartmentalization in the central nervous system. Furthermore, proportion and distribution of resistance mutations to nucleoside and non-nucleoside reverse transcriptase inhibitors differed among different brain areas of the same case suggesting that penetration of antiretroviral treatment may differ from one compartment to another. CONCLUSION: This study, performed with a powerful sequencing technique, confirmed HIV compartmentalization in the central nervous system already shown by classical sequencing, suggesting that there are several reservoirs within the brain.
OBJECTIVES: To examine viral diversity and resistance mutations in different brain areas in cases of HIV-encephalopathy. DESIGN: Twelve postmortem brain areas from three cases of possible or certain HIV-encephalopathy were analyzed. METHODS: After amplification of the reverse transcriptase and the V3 loop region of the gp120 protein, ultradeep sequencing was performed with Illumina technology. Phylogenetic analysis was performed with Fastree v2.1 using the generalized time-reversible (GTR) model. Identification of resistant viral variants was performed on Geneious software, according to HIV-1 genotypic drug resistance interpretation's algorithms, 2018 administered by the French Agency for Research on AIDS and Viral Hepatitis. RESULTS: Phylogenetic analysis revealed significant inter-regional and intra-regional diversity reflecting persistent HIV-1 viral replication in the different brain areas. Although some cerebral regions shared HIV-variants, most of them harbored a specific HIV-subpopulation reflecting HIV compartmentalization in the central nervous system. Furthermore, proportion and distribution of resistance mutations to nucleoside and non-nucleoside reverse transcriptase inhibitors differed among different brain areas of the same case suggesting that penetration of antiretroviral treatment may differ from one compartment to another. CONCLUSION: This study, performed with a powerful sequencing technique, confirmed HIV compartmentalization in the central nervous system already shown by classical sequencing, suggesting that there are several reservoirs within the brain.
Authors: Patricia K Riggs; Antoine Chaillon; Guochun Jiang; Scott L Letendre; Yuyang Tang; Jeff Taylor; Andrew Kaytes; Davey M Smith; Karine Dubé; Sara Gianella Journal: Curr HIV/AIDS Rep Date: 2022-10-19 Impact factor: 5.495
Authors: A Mancon; A Rizzo; D Mileto; S Grosso; A Foschi; M Cutrera; A Capetti; I Faggion; A Anselmo; A Monte; S Fillo; G Rizzardini; M R Gismondo; V Micheli Journal: Emerg Microbes Infect Date: 2022-12 Impact factor: 7.163