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Human Immunodeficiency Virus Type 2 Vpx-mediated Degradation of TASOR Activates Innate Immune Sensing of Nucleic Acids in Infected Cells.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Human Immunodeficiency Virus Type 2 Vpx-mediated Degradation of TASOR Activates Innate Immune Sensing of Nucleic Acids in Infected Cells.
Συγγραφείς: Hanson HM; Molecular, Cellular, Developmental Biology & Genetics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA., Damkot MR; Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA., Mansky LM; Molecular, Cellular, Developmental Biology & Genetics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Diagnostic & Biological Sciences, School of Dentistry, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA. Electronic address: mansky@umn.edu.
Πηγή: Journal of molecular biology [J Mol Biol] 2026 Oct 01; Vol. 438 (19), pp. 169879. Date of Electronic Publication: 2026 May 25.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 2985088R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1089-8638 (Electronic) Linking ISSN: 00222836 NLM ISO Abbreviation: J Mol Biol Subsets: MEDLINE
Imprint Name(s): Publication: Amsterdam : Elsevier
Original Publication: 1959- : London : Academic Press
Ιατρικοί όροι (MeSH): Viral Regulatory and Accessory Proteins*/metabolism , Viral Regulatory and Accessory Proteins*/genetics , HIV-2*/immunology , HIV-2*/genetics , HIV Infections*/virology , HIV Infections*/immunology , HIV Infections*/genetics , HIV Infections*/metabolism , Immunity, Innate*, SAM Domain and HD Domain-Containing Protein 1/metabolism ; Host-Pathogen Interactions/immunology ; Humans ; cGAS-STING Signaling Pathway ; Virus Replication ; Innate Immunity Recognition ; THP-1 Cells
Περίληψη: The HIV-2/SIVsm lineage of lentiviruses encodes for Vpx, which is a virus-associated protein that is absent from HIV-1. Vpx enhances HIV-2 replication by degrading host proteins that possess antiviral activity. For example, Vpx is known to degrade the host dNTPase SAMHD1 (which reduces dNTP levels to inhibit viral DNA synthesis in macrophages) and components of the epigenetic regulator complex HUSH (where degradation enhances proviral gene expression and viral replication). Here, we used a transcriptomic analysis to investigate host gene expression response to HIV-2 infection of THP-1 cells in the presence and absence of Vpx. Analysis of HIV-2 WT and ΔVpx infected cells revealed an increase of gene expression of several interferon stimulating genes (ISGs), with an increase in ISG expression in HIV-2 WT infected cells relative to that of HIV-2 ΔVpx infected cells. Analysis of Vpx mutants implicated that Vpx-mediated induction of ISG expression was due to Vpx-mediated degradation of TASOR, one protein of the HUSH complex. Based upon these observations, we sought to determine whether Vpx-mediated degradation of TASOR and subsequent inhibition of HUSH complex activity induces ISG expression. We found that TASOR degradation by Vpx led to increased LINE-1 activity. Furthermore, we found that Vpx-mediated ISG induction relied on both RNA sensing that was mediated by MAVS signaling and DNA sensing mediated by cGAS/STING signaling. Taken together, these findings support a model in which Vpx-mediated inhibition of the HUSH complex is a key variable how Vpx affects the host response to HIV-2 replication in monocytic cells.
(Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References: J Virol. 2016 Aug 26;90(18):8074-84. (PMID: 27356903)
Retrovirology. 2022 Jan 24;19(1):2. (PMID: 35073912)
Lancet. 1994 Apr 16;343(8903):943-6. (PMID: 7909009)
Retrovirology. 2021 Feb 9;18(1):4. (PMID: 33563288)
Nat Microbiol. 2018 Dec;3(12):1354-1361. (PMID: 30297740)
Nat Microbiol. 2018 Aug;3(8):891-897. (PMID: 29891865)
J Virol. 1990 Feb;64(2):742-7. (PMID: 2296082)
Mol Biol Cell. 2020 Feb 15;31(4):304-317. (PMID: 31913756)
Nat Commun. 2024 Nov 3;15(1):9492. (PMID: 39489739)
Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):2729-2734. (PMID: 28228523)
EBioMedicine. 2016 Jun;8:184-194. (PMID: 27428429)
Curr Infect Dis Rep. 2007 Jul;9(4):338-46. (PMID: 17618555)
Nature. 2018 Jan 11;553(7687):228-232. (PMID: 29211708)
Elife. 2019 Feb 05;8:. (PMID: 30717826)
Genome Res. 2018 Jun;28(6):836-845. (PMID: 29728366)
Nature. 2006 Nov 9;444(7116):164. (PMID: 17093443)
Nat Genet. 2017 Jul;49(7):1035-1044. (PMID: 28581500)
J Virol. 2010 Feb;84(3):1464-76. (PMID: 19906908)
Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):E1343-52. (PMID: 25733890)
PLoS Pathog. 2011 Dec;7(12):e1002425. (PMID: 22174685)
Cell. 2006 Mar 24;124(6):1283-98. (PMID: 16564017)
Science. 2006 Jul 28;313(5786):523-6. (PMID: 16728595)
AIDS. 2000 Mar 10;14(4):441-8. (PMID: 10770548)
Mol Cell. 2024 Aug 8;84(15):2870-2881.e5. (PMID: 39013473)
Int J Mol Sci. 2025 Apr 08;26(8):. (PMID: 40331967)
J Autoimmun. 2018 Jun;90:105-115. (PMID: 29525183)
Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006841. (PMID: 22229120)
Nat Commun. 2020 Nov 3;11(1):5387. (PMID: 33144593)
J Virol. 2017 Mar 29;91(8):. (PMID: 28148784)
J Virol. 2015 May;89(10):5701-13. (PMID: 25762741)
Science. 2015 Jun 26;348(6242):1481-1485. (PMID: 26022416)
Nature. 2011 Jun 29;474(7353):658-61. (PMID: 21720370)
J Gen Virol. 2014 Dec;95(Pt 12):2778-2783. (PMID: 25103850)
JAMA. 1994 Aug 10;272(6):462-6. (PMID: 8040982)
Genes Dev. 2019 Sep 1;33(17-18):1175-1190. (PMID: 31395742)
Science. 2005 Feb 18;307(5712):1098-101. (PMID: 15718470)
Dev Neurobiol. 2018 May;78(5):434-455. (PMID: 29239145)
Trends Microbiol. 2019 Mar;27(3):254-267. (PMID: 30336972)
J Virol. 2025 May 20;99(5):e0019825. (PMID: 40261013)
Grant Information: F31 AI147805 United States AI NIAID NIH HHS; R01 AI177264 United States AI NIAID NIH HHS; T32 AI083196 United States AI NIAID NIH HHS
Contributed Indexing: Keywords: acquired immunodeficiency syndrome; lentivirus; transcriptome
Substance Nomenclature: 0 (VPX protein, Human immunodeficiency virus 2)
0 (Viral Regulatory and Accessory Proteins)
EC 3.1.5.- (SAM Domain and HD Domain-Containing Protein 1)
Entry Date(s): Date Created: 20260526 Date Completed: 20260806 Latest Revision: 20260922
Update Code: 20260922
PubMed Central ID: PMC13382530
DOI: 10.1016/j.jmb.2026.169879
PMID: 42190982
Βάση Δεδομένων: MEDLINE
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  Data: Human Immunodeficiency Virus Type 2 Vpx-mediated Degradation of TASOR Activates Innate Immune Sensing of Nucleic Acids in Infected Cells.
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  Data: <searchLink fieldCode="AU" term="%22Hanson+HM%22">Hanson HM</searchLink>; Molecular, Cellular, Developmental Biology & Genetics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.<br /><searchLink fieldCode="AU" term="%22Damkot+MR%22">Damkot MR</searchLink>; Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.<br /><searchLink fieldCode="AU" term="%22Mansky+LM%22">Mansky LM</searchLink>; Molecular, Cellular, Developmental Biology & Genetics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Diagnostic & Biological Sciences, School of Dentistry, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA. Electronic address: mansky@umn.edu.
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  Data: The HIV-2/SIV<subscript>sm</subscript> lineage of lentiviruses encodes for Vpx, which is a virus-associated protein that is absent from HIV-1. Vpx enhances HIV-2 replication by degrading host proteins that possess antiviral activity. For example, Vpx is known to degrade the host dNTPase SAMHD1 (which reduces dNTP levels to inhibit viral DNA synthesis in macrophages) and components of the epigenetic regulator complex HUSH (where degradation enhances proviral gene expression and viral replication). Here, we used a transcriptomic analysis to investigate host gene expression response to HIV-2 infection of THP-1 cells in the presence and absence of Vpx. Analysis of HIV-2 WT and ΔVpx infected cells revealed an increase of gene expression of several interferon stimulating genes (ISGs), with an increase in ISG expression in HIV-2 WT infected cells relative to that of HIV-2 ΔVpx infected cells. Analysis of Vpx mutants implicated that Vpx-mediated induction of ISG expression was due to Vpx-mediated degradation of TASOR, one protein of the HUSH complex. Based upon these observations, we sought to determine whether Vpx-mediated degradation of TASOR and subsequent inhibition of HUSH complex activity induces ISG expression. We found that TASOR degradation by Vpx led to increased LINE-1 activity. Furthermore, we found that Vpx-mediated ISG induction relied on both RNA sensing that was mediated by MAVS signaling and DNA sensing mediated by cGAS/STING signaling. Taken together, these findings support a model in which Vpx-mediated inhibition of the HUSH complex is a key variable how Vpx affects the host response to HIV-2 replication in monocytic cells.<br /> (Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
– Name: Ref
  Label: References
  Group: RefInfo
  Data: J Virol. 2016 Aug 26;90(18):8074-84. (PMID: <searchLink fieldCode="PM" term="%2227356903%22">27356903)</searchLink><br />Retrovirology. 2022 Jan 24;19(1):2. (PMID: <searchLink fieldCode="PM" term="%2235073912%22">35073912)</searchLink><br />Lancet. 1994 Apr 16;343(8903):943-6. (PMID: <searchLink fieldCode="PM" term="%227909009%22">7909009)</searchLink><br />Retrovirology. 2021 Feb 9;18(1):4. (PMID: <searchLink fieldCode="PM" term="%2233563288%22">33563288)</searchLink><br />Nat Microbiol. 2018 Dec;3(12):1354-1361. (PMID: <searchLink fieldCode="PM" term="%2230297740%22">30297740)</searchLink><br />Nat Microbiol. 2018 Aug;3(8):891-897. (PMID: <searchLink fieldCode="PM" term="%2229891865%22">29891865)</searchLink><br />J Virol. 1990 Feb;64(2):742-7. (PMID: <searchLink fieldCode="PM" term="%222296082%22">2296082)</searchLink><br />Mol Biol Cell. 2020 Feb 15;31(4):304-317. (PMID: <searchLink fieldCode="PM" term="%2231913756%22">31913756)</searchLink><br />Nat Commun. 2024 Nov 3;15(1):9492. (PMID: <searchLink fieldCode="PM" term="%2239489739%22">39489739)</searchLink><br />Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):2729-2734. (PMID: <searchLink fieldCode="PM" term="%2228228523%22">28228523)</searchLink><br />EBioMedicine. 2016 Jun;8:184-194. (PMID: <searchLink fieldCode="PM" term="%2227428429%22">27428429)</searchLink><br />Curr Infect Dis Rep. 2007 Jul;9(4):338-46. (PMID: <searchLink fieldCode="PM" term="%2217618555%22">17618555)</searchLink><br />Nature. 2018 Jan 11;553(7687):228-232. (PMID: <searchLink fieldCode="PM" term="%2229211708%22">29211708)</searchLink><br />Elife. 2019 Feb 05;8:. (PMID: <searchLink fieldCode="PM" term="%2230717826%22">30717826)</searchLink><br />Genome Res. 2018 Jun;28(6):836-845. (PMID: <searchLink fieldCode="PM" term="%2229728366%22">29728366)</searchLink><br />Nature. 2006 Nov 9;444(7116):164. (PMID: <searchLink fieldCode="PM" term="%2217093443%22">17093443)</searchLink><br />Nat Genet. 2017 Jul;49(7):1035-1044. (PMID: <searchLink fieldCode="PM" term="%2228581500%22">28581500)</searchLink><br />J Virol. 2010 Feb;84(3):1464-76. (PMID: <searchLink fieldCode="PM" term="%2219906908%22">19906908)</searchLink><br />Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):E1343-52. (PMID: <searchLink fieldCode="PM" term="%2225733890%22">25733890)</searchLink><br />PLoS Pathog. 2011 Dec;7(12):e1002425. (PMID: <searchLink fieldCode="PM" term="%2222174685%22">22174685)</searchLink><br />Cell. 2006 Mar 24;124(6):1283-98. (PMID: <searchLink fieldCode="PM" term="%2216564017%22">16564017)</searchLink><br />Science. 2006 Jul 28;313(5786):523-6. (PMID: <searchLink fieldCode="PM" term="%2216728595%22">16728595)</searchLink><br />AIDS. 2000 Mar 10;14(4):441-8. (PMID: <searchLink fieldCode="PM" term="%2210770548%22">10770548)</searchLink><br />Mol Cell. 2024 Aug 8;84(15):2870-2881.e5. (PMID: <searchLink fieldCode="PM" term="%2239013473%22">39013473)</searchLink><br />Int J Mol Sci. 2025 Apr 08;26(8):. (PMID: <searchLink fieldCode="PM" term="%2240331967%22">40331967)</searchLink><br />J Autoimmun. 2018 Jun;90:105-115. (PMID: <searchLink fieldCode="PM" term="%2229525183%22">29525183)</searchLink><br />Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006841. (PMID: <searchLink fieldCode="PM" term="%2222229120%22">22229120)</searchLink><br />Nat Commun. 2020 Nov 3;11(1):5387. (PMID: <searchLink fieldCode="PM" term="%2233144593%22">33144593)</searchLink><br />J Virol. 2017 Mar 29;91(8):. (PMID: <searchLink fieldCode="PM" term="%2228148784%22">28148784)</searchLink><br />J Virol. 2015 May;89(10):5701-13. (PMID: <searchLink fieldCode="PM" term="%2225762741%22">25762741)</searchLink><br />Science. 2015 Jun 26;348(6242):1481-1485. (PMID: <searchLink fieldCode="PM" term="%2226022416%22">26022416)</searchLink><br />Nature. 2011 Jun 29;474(7353):658-61. (PMID: <searchLink fieldCode="PM" term="%2221720370%22">21720370)</searchLink><br />J Gen Virol. 2014 Dec;95(Pt 12):2778-2783. (PMID: <searchLink fieldCode="PM" term="%2225103850%22">25103850)</searchLink><br />JAMA. 1994 Aug 10;272(6):462-6. (PMID: <searchLink fieldCode="PM" term="%228040982%22">8040982)</searchLink><br />Genes Dev. 2019 Sep 1;33(17-18):1175-1190. (PMID: <searchLink fieldCode="PM" term="%2231395742%22">31395742)</searchLink><br />Science. 2005 Feb 18;307(5712):1098-101. (PMID: <searchLink fieldCode="PM" term="%2215718470%22">15718470)</searchLink><br />Dev Neurobiol. 2018 May;78(5):434-455. (PMID: <searchLink fieldCode="PM" term="%2229239145%22">29239145)</searchLink><br />Trends Microbiol. 2019 Mar;27(3):254-267. (PMID: <searchLink fieldCode="PM" term="%2230336972%22">30336972)</searchLink><br />J Virol. 2025 May 20;99(5):e0019825. (PMID: <searchLink fieldCode="PM" term="%2240261013%22">40261013)</searchLink>
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  Data: <i>Keywords: </i>acquired immunodeficiency syndrome; lentivirus; transcriptome
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      – SubjectFull: SAM Domain and HD Domain-Containing Protein 1 metabolism
        Type: general
      – SubjectFull: Host-Pathogen Interactions immunology
        Type: general
      – SubjectFull: Humans
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      – SubjectFull: cGAS-STING Signaling Pathway
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      – SubjectFull: Viral Regulatory and Accessory Proteins metabolism
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      – SubjectFull: HIV Infections immunology
        Type: general
      – SubjectFull: HIV Infections genetics
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      – SubjectFull: HIV Infections metabolism
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      – SubjectFull: Immunity, Innate
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      – TitleFull: Human Immunodeficiency Virus Type 2 Vpx-mediated Degradation of TASOR Activates Innate Immune Sensing of Nucleic Acids in Infected Cells.
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      – BibEntity:
          Dates:
            – D: 01
              M: 10
              Text: 2026 Oct 01
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1089-8638
          Numbering:
            – Type: volume
              Value: 438
            – Type: issue
              Value: 19
          Titles:
            – TitleFull: Journal of molecular biology
              Type: main
ResultId 1