Dataset Information

Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection.

ABSTRACT: HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder (T/F) viruses differ between CNS and blood during AHI using single-genome sequencing of envelope gene and further examined subregions in pol and env using next-generation sequencing in paired plasma and cerebrospinal fluid (CSF) from 18 individuals. Different proportions of mostly minor variants were found in six of the eight multiple T/F-infected individuals, indicating enrichment of some variants in CSF that may lead to significant compartmentalization in the later stages of infection. This study provides evidence for the first time that HIV-1 compartmentalization in the CNS can occur within days of HIV-1 exposure in multiple T/F infections. Further understanding of factors that determine enrichment of T/F variants in the CNS, as well as potential long-term implications of these findings for persistence of HIV-1 reservoirs and neurological impairment in HIV, is needed.

SUBMITTER: Tovanabutra S

PROVIDER: S-EPMC6721674 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection.

Tovanabutra Sodsai S Sirijatuphat Rujipas R Pham Phuc T PT Bonar Lydia L Harbolick Elizabeth A EA Bose Meera M Song Hongshuo H Chang David D Oropeza Celina C O'Sullivan Anne Marie AM Balinang Joyce J Kroon Eugene E Colby Donn J DJ Sacdalan Carlo C Hellmuth Joanna J Chan Phillip P Prueksakaew Peeriya P Pinyakorn Suteeraporn S Jagodzinski Linda L LL Sutthichom Duanghathai D Pattamaswin Suwanna S de Souza Mark M Gramzinski Robert A RA Kim Jerome H JH Michael Nelson L NL Robb Merlin L ML Phanuphak Nittaya N Ananworanich Jintanat J Valcour Victor V Kijak Gustavo H GH Sanders-Buell Eric E Spudich Serena S

Cells 20190815 8

HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder ...[more]

PMID: 31443253

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Dataset Information

Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection.

Publications

Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection.

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