Ultradeep sequencing reveals HIV-1 diversity and resistance compartmentalization during HIV-encephalopathy
| Autor: | Nathalie Désiré, Isabelle Plu, Vincent Calvez, Romain Palich, Anne-Geneviève Marcelin, Eleni Giatsou, Danielle Seilhean, Basma Abdi, Aude Jary |
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| Rok vydání: | 2020 |
| Předmět: |
AIDS Dementia Complex
Genotype Anti-HIV Agents Immunology HIV Infections Drug resistance HIV Envelope Protein gp120 V3 loop Biology 03 medical and health sciences 0302 clinical medicine Acquired immunodeficiency syndrome (AIDS) Drug Resistance Viral medicine Humans Immunology and Allergy Amplified Fragment Length Polymorphism Analysis Phylogeny 030304 developmental biology Genetics 0303 health sciences Phylogenetic tree Reverse Transcriptase Polymerase Chain Reaction High-Throughput Nucleotide Sequencing medicine.disease Reverse transcriptase 3. Good health Infectious Diseases Anti-Retroviral Agents Viral replication Mutation HIV-1 Viral hepatitis 030217 neurology & neurosurgery |
| Zdroj: | AIDS. 34:1609-1614 |
| ISSN: | 1473-5571 0269-9370 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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