Vpx and Vpr proteins of HIV-2 up-regulate the viral infectivity by a distinct mechanism in lymphocytic cells

Ueno, Fumiko; Shiota, Hiroshi; Miyaura, Maki; Yoshida, Akira; Sakurai, Akiko; Tatsuki, Junko; Koyama, A. Hajime; Akari, Hirofumi; Adachi, Akio; Fujita, Mikako

doi:10.1016/s1286-4579(03)00042-x

Cited by 42 publications

(72 citation statements)

References 48 publications

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“…Since both Vpr and Vpx recruit DCAF1, silencing of DCAF1 might have interfered with Vpr rather than Vpx function. However, in agreement with previous studies of HIV-2 and SIVsm/mac (9,32,48), HIV-2 replication in macrophages was only mildly affected by Vpr deletion compared to Vpx deletion (see Fig. S1 in the supplemental material).…”

Section: Resultssupporting

confidence: 92%

“…Conflicting data have been reported on the role of Vpx in HIV-2 infection of lymphoid cells using T-cell lines or peripheral blood mononuclear cells (13,19,22,23,48). However, we have not observed a dependence on Vpx in primary CD4 T-lymphocyte infection by HIV-2.…”

Section: Discussioncontrasting

confidence: 88%

“…The pGL-AN plasmid, which carries a replication-competent HIV-2 provirus from the GH-1 isolate, as well as its derivatives defective in the Vpr and/or the Vpx genes (48), were kindly provided by A. Adachi. Env-defective viruses were obtained by creating a frameshift mutation at the unique NsiI site as previously described (48). To create a HIV-2 proviral clone encoding the Vpx Q76 mutant, the 400-bp SacI fragment of pGL-AN that overlaps the 3Ј and 5Ј sequences of the vpx and vpr genes was subcloned into PUC19 prior to site-directed mutagenesis, and the mutagenized fragment was cloned back into the HIV-2 backbone.…”

Section: Methodsmentioning

confidence: 99%

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The Human Immunodeficiency Virus Type 2 Vpx Protein Usurps the CUL4A-DDB1 ^DCAF1 Ubiquitin Ligase To Overcome a Postentry Block in Macrophage Infection

Bergamaschi

Ayinde

David

et al. 2009

J Virol

113

120

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The human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) genomes encode several auxiliary proteins that have increasingly shown their importance in the virus-host relationship. One of these proteins, Vpx, is unique to the HIV-2/SIVsm lineage and is critical for viral replication in macrophages. The functional basis for this requirement, as well as the Vpx mode of action, has remained unexplained, and it is all the more enigmatic that HIV type 1 (HIV-1), which has no Vpx counterpart, can infect macrophages. Here, we underscore DCAF1 as a critical host effector of Vpx in its ability to mediate infection and long-term replication of HIV-2 in human macrophages. Vpx assembles with the CUL4A-DDB1 ubiquitin ligase through DCAF1 recruitment. Precluding Vpx present in the incoming virions from recruiting DCAF1 in target macrophages leads to a postentry block characterized by defective accumulation of HIV-2 reverse transcripts. In addition, Vpx from SIVsm functionally complements Vpx-defective HIV-2 in a DCAF1-binding-dependent manner. Altogether, our data point to a mechanism in which Vpx diverts the Cul4A-DDB1 DCAF1 ligase to inactivate an evolutionarily conserved factor, which restricts macrophage infection by HIV-2 and closely related simian viruses.

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Section: Resultssupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Human Immunodeficiency Virus Type 2 Vpx Protein Usurps the CUL4A-DDB1 ^DCAF1 Ubiquitin Ligase To Overcome a Postentry Block in Macrophage Infection

Bergamaschi

Ayinde

David

et al. 2009

J Virol

113

120

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“…However, despite these reports, the exact function of Vpx remains debated, as a few studies failed to reveal a nuclear localization of Vpx (22,46), while others also reported a requirement for Vpx in the infection of cycling cells, suggesting a role distinct from nuclear import (2,14,18,21,23,33,43,47).…”

Section: Human Immunodeficiency Virus Type 2 (Hiv-2)/simian Immunodefmentioning

confidence: 99%

“…The replication-competent HIV-2 GL-AN proviral clone was obtained from A. Adachi (Tokushima, Japan) and was described elsewhere previously (43). Mutations were introduced by standard mutagenesis within the XbaI/NsiI fragment spanning vpx (nucleotides 5072 to 6264 according to sequence reported under GenBank accession no.…”

Section: Cellsmentioning

confidence: 99%

Characterization of Simian Immunodeficiency Virus SIV _SM /Human Immunodeficiency Virus Type 2 Vpx Function in Human Myeloid Cells

Goujon

Arfi

Pertel

et al. 2008

J Virol

121

140

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Introduction of H2C2‐type zinc‐binding residues into HIV‐2 Vpr increases its expression level

et al. 2017

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Human immunodeficiency virus type 2 has two structurally similar proteins, Vpx and Vpr. Vpx degrades the host anti‐viral protein SAMHD1 and is expressed at high levels, while Vpr is responsible for cell cycle arrest and is expressed at much lower levels. We constructed a Vpr mutant with a high level of expression by replacing the amino acids HHCR/HHCH with a putative H2C2‐type zinc‐binding site that is carried by Vpx. Our finding suggests that during the evolution of Vpr and Vpx, zinc‐binding likely became a mechanism for regulating their expression levels.

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Vpx and Vpr proteins of HIV-2 up-regulate the viral infectivity by a distinct mechanism in lymphocytic cells

Cited by 42 publications

References 48 publications

The Human Immunodeficiency Virus Type 2 Vpx Protein Usurps the CUL4A-DDB1 ^DCAF1 Ubiquitin Ligase To Overcome a Postentry Block in Macrophage Infection

The Human Immunodeficiency Virus Type 2 Vpx Protein Usurps the CUL4A-DDB1 ^DCAF1 Ubiquitin Ligase To Overcome a Postentry Block in Macrophage Infection

Characterization of Simian Immunodeficiency Virus SIV _SM /Human Immunodeficiency Virus Type 2 Vpx Function in Human Myeloid Cells

Introduction of H2C2‐type zinc‐binding residues into HIV‐2 Vpr increases its expression level

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Vpx and Vpr proteins of HIV-2 up-regulate the viral infectivity by a distinct mechanism in lymphocytic cells

Cited by 42 publications

References 48 publications

The Human Immunodeficiency Virus Type 2 Vpx Protein Usurps the CUL4A-DDB1 DCAF1 Ubiquitin Ligase To Overcome a Postentry Block in Macrophage Infection

The Human Immunodeficiency Virus Type 2 Vpx Protein Usurps the CUL4A-DDB1 DCAF1 Ubiquitin Ligase To Overcome a Postentry Block in Macrophage Infection

Characterization of Simian Immunodeficiency Virus SIV SM /Human Immunodeficiency Virus Type 2 Vpx Function in Human Myeloid Cells

Introduction of H2C2‐type zinc‐binding residues into HIV‐2 Vpr increases its expression level

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The Human Immunodeficiency Virus Type 2 Vpx Protein Usurps the CUL4A-DDB1 ^DCAF1 Ubiquitin Ligase To Overcome a Postentry Block in Macrophage Infection

The Human Immunodeficiency Virus Type 2 Vpx Protein Usurps the CUL4A-DDB1 ^DCAF1 Ubiquitin Ligase To Overcome a Postentry Block in Macrophage Infection

Characterization of Simian Immunodeficiency Virus SIV _SM /Human Immunodeficiency Virus Type 2 Vpx Function in Human Myeloid Cells