HHV-6B ribonucleotide reductase sequesters NF-κB subunit p65 to inhibit innate immune responses
Summary: Human herpesvirus 6B (HHV-6B) belongs to the genus Roseolovirus of the betaherpesvirus subfamily, causing exanthema subitum and encephalitis. Although viral ribonucleotide reductase (RNR) is conserved in betaherpesviruses, it has lost its enzymatic activity. Human cytomegalovirus (HCMV) bel...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224029377 |
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| author | Mansaku Hirai Khoir Amaliin Jing Rin Huang Salma Aktar Yasuko Mori Jun Arii |
| author_facet | Mansaku Hirai Khoir Amaliin Jing Rin Huang Salma Aktar Yasuko Mori Jun Arii |
| author_sort | Mansaku Hirai |
| collection | DOAJ |
| description | Summary: Human herpesvirus 6B (HHV-6B) belongs to the genus Roseolovirus of the betaherpesvirus subfamily, causing exanthema subitum and encephalitis. Although viral ribonucleotide reductase (RNR) is conserved in betaherpesviruses, it has lost its enzymatic activity. Human cytomegalovirus (HCMV) belongs to the other betaherpesvirus genus, Cytomegalovirus; its RNR inhibits nuclear factor-kappa B (NF-κB) signaling via interaction with the adaptor molecule RIPK1. However, the significance of enzymatically inactive RNR in roseoviruses is unclear. Here, we show that the RNRs from all three human roseoloviruses inhibit NF-κB activation. HHV-6B RNR sequesters NF-κB subunit p65 in the cytoplasm and inhibits its translocation into the nucleus. Silencing HHV-6B RNR increased the expression of inflammatory molecules in infected cells. This study reveals that inhibiting NF-κB is a conserved role of the RNR in betaherpesviruses but that the precise mechanisms responsible for these effects are different. |
| format | Article |
| id | doaj-art-39a2fd034dfc418bb0673a0684e93951 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-39a2fd034dfc418bb0673a0684e939512025-01-13T04:19:05ZengElsevieriScience2589-00422025-02-01282111710HHV-6B ribonucleotide reductase sequesters NF-κB subunit p65 to inhibit innate immune responsesMansaku Hirai0Khoir Amaliin1Jing Rin Huang2Salma Aktar3Yasuko Mori4Jun Arii5Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo, JapanDivision of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo, JapanDivision of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo, JapanDivision of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo, JapanDivision of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo, JapanDivision of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan; Corresponding authorSummary: Human herpesvirus 6B (HHV-6B) belongs to the genus Roseolovirus of the betaherpesvirus subfamily, causing exanthema subitum and encephalitis. Although viral ribonucleotide reductase (RNR) is conserved in betaherpesviruses, it has lost its enzymatic activity. Human cytomegalovirus (HCMV) belongs to the other betaherpesvirus genus, Cytomegalovirus; its RNR inhibits nuclear factor-kappa B (NF-κB) signaling via interaction with the adaptor molecule RIPK1. However, the significance of enzymatically inactive RNR in roseoviruses is unclear. Here, we show that the RNRs from all three human roseoloviruses inhibit NF-κB activation. HHV-6B RNR sequesters NF-κB subunit p65 in the cytoplasm and inhibits its translocation into the nucleus. Silencing HHV-6B RNR increased the expression of inflammatory molecules in infected cells. This study reveals that inhibiting NF-κB is a conserved role of the RNR in betaherpesviruses but that the precise mechanisms responsible for these effects are different.http://www.sciencedirect.com/science/article/pii/S2589004224029377Cell biologyImmunologyVirology |
| spellingShingle | Mansaku Hirai Khoir Amaliin Jing Rin Huang Salma Aktar Yasuko Mori Jun Arii HHV-6B ribonucleotide reductase sequesters NF-κB subunit p65 to inhibit innate immune responses iScience Cell biology Immunology Virology |
| title | HHV-6B ribonucleotide reductase sequesters NF-κB subunit p65 to inhibit innate immune responses |
| title_full | HHV-6B ribonucleotide reductase sequesters NF-κB subunit p65 to inhibit innate immune responses |
| title_fullStr | HHV-6B ribonucleotide reductase sequesters NF-κB subunit p65 to inhibit innate immune responses |
| title_full_unstemmed | HHV-6B ribonucleotide reductase sequesters NF-κB subunit p65 to inhibit innate immune responses |
| title_short | HHV-6B ribonucleotide reductase sequesters NF-κB subunit p65 to inhibit innate immune responses |
| title_sort | hhv 6b ribonucleotide reductase sequesters nf κb subunit p65 to inhibit innate immune responses |
| topic | Cell biology Immunology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224029377 |
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