The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells.
For nearly 20 years, the principal biological function of the HIV-2/SIV Vpx gene has been thought to be required for optimal virus replication in myeloid cells. Mechanistically, this Vpx activity was recently reported to involve the degradation of Sterile Alpha Motif and HD domain-containing protein...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-05-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4440783?pdf=render |
| _version_ | 1819038172024143872 |
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| author | Masashi Shingai Sarah Welbourn Jason M Brenchley Priyamvada Acharya Eri Miyagi Ronald J Plishka Alicia Buckler-White Peter D Kwong Yoshiaki Nishimura Klaus Strebel Malcolm A Martin |
| author_facet | Masashi Shingai Sarah Welbourn Jason M Brenchley Priyamvada Acharya Eri Miyagi Ronald J Plishka Alicia Buckler-White Peter D Kwong Yoshiaki Nishimura Klaus Strebel Malcolm A Martin |
| author_sort | Masashi Shingai |
| collection | DOAJ |
| description | For nearly 20 years, the principal biological function of the HIV-2/SIV Vpx gene has been thought to be required for optimal virus replication in myeloid cells. Mechanistically, this Vpx activity was recently reported to involve the degradation of Sterile Alpha Motif and HD domain-containing protein 1 (SAMHD1) in this cell lineage. Here we show that when macaques were inoculated with either the T cell tropic SIVmac239 or the macrophage tropic SIVmac316 carrying a Vpx point mutation that abrogates the recruitment of DCAF1 and the ensuing degradation of endogenous SAMHD1 in cultured CD4+ T cells, virus acquisition, progeny virion production in memory CD4+ T cells during acute infection, and the maintenance of set-point viremia were greatly attenuated. Revertant viruses emerging in two animals exhibited an augmented replication phenotype in memory CD4+ T lymphocytes both in vitro and in vivo, which was associated with reduced levels of endogenous SAMHD1. These results indicate that a critical role of Vpx in vivo is to promote the degradation of SAMHD1 in memory CD4+ T lymphocytes, thereby generating high levels of plasma viremia and the induction of immunodeficiency. |
| first_indexed | 2024-12-21T08:33:05Z |
| format | Article |
| id | doaj.art-7382312e0a5a4f02aaf32f1c7b3281aa |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T08:33:05Z |
| publishDate | 2015-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-7382312e0a5a4f02aaf32f1c7b3281aa2022-12-21T19:10:08ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-05-01115e100492810.1371/journal.ppat.1004928The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells.Masashi ShingaiSarah WelbournJason M BrenchleyPriyamvada AcharyaEri MiyagiRonald J PlishkaAlicia Buckler-WhitePeter D KwongYoshiaki NishimuraKlaus StrebelMalcolm A MartinFor nearly 20 years, the principal biological function of the HIV-2/SIV Vpx gene has been thought to be required for optimal virus replication in myeloid cells. Mechanistically, this Vpx activity was recently reported to involve the degradation of Sterile Alpha Motif and HD domain-containing protein 1 (SAMHD1) in this cell lineage. Here we show that when macaques were inoculated with either the T cell tropic SIVmac239 or the macrophage tropic SIVmac316 carrying a Vpx point mutation that abrogates the recruitment of DCAF1 and the ensuing degradation of endogenous SAMHD1 in cultured CD4+ T cells, virus acquisition, progeny virion production in memory CD4+ T cells during acute infection, and the maintenance of set-point viremia were greatly attenuated. Revertant viruses emerging in two animals exhibited an augmented replication phenotype in memory CD4+ T lymphocytes both in vitro and in vivo, which was associated with reduced levels of endogenous SAMHD1. These results indicate that a critical role of Vpx in vivo is to promote the degradation of SAMHD1 in memory CD4+ T lymphocytes, thereby generating high levels of plasma viremia and the induction of immunodeficiency.http://europepmc.org/articles/PMC4440783?pdf=render |
| spellingShingle | Masashi Shingai Sarah Welbourn Jason M Brenchley Priyamvada Acharya Eri Miyagi Ronald J Plishka Alicia Buckler-White Peter D Kwong Yoshiaki Nishimura Klaus Strebel Malcolm A Martin The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells. PLoS Pathogens |
| title | The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells. |
| title_full | The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells. |
| title_fullStr | The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells. |
| title_full_unstemmed | The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells. |
| title_short | The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells. |
| title_sort | expression of functional vpx during pathogenic sivmac infections of rhesus macaques suppresses samhd1 in cd4 memory t cells |
| url | http://europepmc.org/articles/PMC4440783?pdf=render |
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