Cells (Aug 2019)
Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection
- Sodsai Tovanabutra,
- Rujipas Sirijatuphat,
- Phuc T. Pham,
- Lydia Bonar,
- Elizabeth A. Harbolick,
- Meera Bose,
- Hongshuo Song,
- David Chang,
- Celina Oropeza,
- Anne Marie O’Sullivan,
- Joyce Balinang,
- Eugene Kroon,
- Donn J. Colby,
- Carlo Sacdalan,
- Joanna Hellmuth,
- Phillip Chan,
- Peeriya Prueksakaew,
- Suteeraporn Pinyakorn,
- Linda L. Jagodzinski,
- Duanghathai Sutthichom,
- Suwanna Pattamaswin,
- Mark de Souza,
- Robert A. Gramzinski,
- Jerome H. Kim,
- Nelson L. Michael,
- Merlin L. Robb,
- Nittaya Phanuphak,
- Jintanat Ananworanich,
- Victor Valcour,
- Gustavo H. Kijak,
- Eric Sanders-Buell,
- Serena Spudich,
- The MHRP Viral Sequencing Core,
- the RV254/SEARCH 010 Study Team
Affiliations
- Sodsai Tovanabutra
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Rujipas Sirijatuphat
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Phuc T. Pham
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Lydia Bonar
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Elizabeth A. Harbolick
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Meera Bose
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Hongshuo Song
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- David Chang
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Celina Oropeza
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Anne Marie O’Sullivan
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Joyce Balinang
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Eugene Kroon
- SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand
- Donn J. Colby
- SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand
- Carlo Sacdalan
- SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand
- Joanna Hellmuth
- Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USA
- Phillip Chan
- SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand
- Peeriya Prueksakaew
- SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand
- Suteeraporn Pinyakorn
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Linda L. Jagodzinski
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Duanghathai Sutthichom
- SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand
- Suwanna Pattamaswin
- SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand
- Mark de Souza
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA
- Robert A. Gramzinski
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Jerome H. Kim
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Nelson L. Michael
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Merlin L. Robb
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Nittaya Phanuphak
- SEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, Thailand
- Jintanat Ananworanich
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Victor Valcour
- Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USA
- Gustavo H. Kijak
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Eric Sanders-Buell
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Serena Spudich
- Department of Neurology, Yale University; New Haven, CT 06510, USA
- The MHRP Viral Sequencing Core
- the RV254/SEARCH 010 Study Team
- DOI
- https://doi.org/10.3390/cells8080902
- Journal volume & issue
-
Vol. 8,
no. 8
p. 902
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.
Keywords
- HIV-1
- central nervous system (CNS)
- cerebrospinal fluid (CSF)
- compartmentalization
- acute HIV-1 infection (AHI)
- transmitted/founder (T/F) virus
- multiple infections
- single-genome amplification (SGA)
- next-generation sequencing (NGS)
