Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection
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 compartm...
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MDPI AG
2019-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/8/8/902 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sodsai Tovanabutra |
| collection | DOAJ |
| description | 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 <i>pol</i> and <i>env</i> 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. |
| first_indexed | 2024-03-12T19:16:04Z |
| format | Article |
| id | doaj.art-549d53bc2b784aa48b5bc7932b75bcd8 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:16:04Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-549d53bc2b784aa48b5bc7932b75bcd82023-08-02T05:30:53ZengMDPI AGCells2073-44092019-08-018890210.3390/cells8080902cells8080902Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 InfectionSodsai Tovanabutra0Rujipas Sirijatuphat1Phuc T. Pham2Lydia Bonar3Elizabeth A. Harbolick4Meera Bose5Hongshuo Song6David Chang7Celina Oropeza8Anne Marie O’Sullivan9Joyce Balinang10Eugene Kroon11Donn J. Colby12Carlo Sacdalan13Joanna Hellmuth14Phillip Chan15Peeriya Prueksakaew16Suteeraporn Pinyakorn17Linda L. Jagodzinski18Duanghathai Sutthichom19Suwanna Pattamaswin20Mark de Souza21Robert A. Gramzinski22Jerome H. Kim23Nelson L. Michael24Merlin L. Robb25Nittaya Phanuphak26Jintanat Ananworanich27Victor Valcour28Gustavo H. Kijak29Eric Sanders-Buell30Serena Spudich31The MHRP Viral Sequencing Corethe RV254/SEARCH 010 Study TeamU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USASEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, ThailandSEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, ThailandSEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, ThailandMemory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USASEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, ThailandSEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, ThailandU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USASEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, ThailandSEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, ThailandThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USASEARCH, Thai Red Cross AIDS Research Centre, Bangkok 10330, ThailandU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAMemory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USADepartment of Neurology, Yale University; New Haven, CT 06510, USAHIV-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 <i>pol</i> and <i>env</i> 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.https://www.mdpi.com/2073-4409/8/8/902HIV-1central nervous system (CNS)cerebrospinal fluid (CSF)compartmentalizationacute HIV-1 infection (AHI)transmitted/founder (T/F) virusmultiple infectionssingle-genome amplification (SGA)next-generation sequencing (NGS) |
| spellingShingle | 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 Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection Cells 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) |
| title | Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection |
| title_full | Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection |
| title_fullStr | Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection |
| title_full_unstemmed | Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection |
| title_short | Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection |
| title_sort | deep sequencing reveals central nervous system compartmentalization in multiple transmitted founder virus acute hiv 1 infection |
| topic | 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) |
| url | https://www.mdpi.com/2073-4409/8/8/902 |
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