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

Goujon, Caroline; Arfi, Vanessa; Pertel, Thomas; Luban, Jeremy; Lienard, Julia; Rigal, Dominique; Darlix, Jean‐Luc; Cimarelli, Andrea

doi:10.1128/jvi.01181-08

Cited by 121 publications

(157 citation statements)

References 49 publications

(89 reference statements)

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“…Knockdown of DCAF-1 was achieved upon transduction of target cells with lentiviral vectors encoding control or DCAF-1 hairpins (22). Briefly, lentivectors were produced by cotransfection of HIV-1 Gag-Pol, VSV-G, and the indicated short hairpin RNA (shRNA) constructs as described previously using the following target sequences: for ShDCAF-1, GCGGACTGGAGGTGATCAT; and for ShControl, AGC TCCCGTGAATTGGAATCC.…”

Section: Methodsmentioning

confidence: 99%

G ₂ /M Cell Cycle Arrest Correlates with Primate Lentiviral Vpr Interaction with the SLX4 Complex

Berger

Lawrence

Hué

et al. 2015

J Virol

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V iral protein R (Vpr) is an accessory protein common to all primate lentiviruses whose role in viral replication remains unclear. It is packaged specifically into virions and is associated with the reverse-transcription complex during early steps of infection (1, 2). Although implicated in various virological processes, the major phenotype ascribed to Vpr is the induction of G 2 /M cell cycle arrest in dividing cells (3, 4). The importance of this phenotype in human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) replication has been notoriously difficult to define because of the minor effects of its deletion on viral replication in cell culture (5). However, reversion of inactivating mutations in both primates and humans highlights that Vpr plays an essential role for viral replication in vivo (6). In addition to cell cycle arrest, several SIV Vpr alleles are capable of targeting the host restriction factor SAMHD1 and that function became separated in the sooty mangabey SIV (SIVsm) lineage upon duplication to generate the vpx gene peculiar to this group (7). Importantly, at present HIV-1 Vpr is not known to retain any SAMHD1 counteractivity (7-10).Vpr-mediated cell cycle arrest depends on its localization to nuclear compartments and the ability to hijack a Cullin-4/DDB1/ Roc1 E3 ubiquitin ligase complex through the WD-containing DCAF-1 adaptor (11,12). For HIV-1 Vpr, this leads ultimately to the activation of the ataxia telangiectasia M and Rad3-related (ATR) and Chk1 kinases to prevent cell cycle progression into mitosis (13). Although several putative Vpr targets have been described, the identity of that which triggers this event has until recently remained elusive. The requirement for the ubiquitin-proteasome system and, in particular, K48-ubiquitin linkages supported a notion that the Vpr target is degraded (14). However, Laguette and colleagues recently found that Vpr interacts with the SLX4 complex, members of the Fanconi anemia DNA repair pathway (15). SLX4, also known as Fanconi anemia complementation group P (FANCP), is a large adaptor protein that acts as a scaffold for a heterodimeric structure-specific endonuclease comprised of MUS81 and EME1. This interaction directs this endonuclease and

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Section: Methodsmentioning

confidence: 99%

G ₂ /M Cell Cycle Arrest Correlates with Primate Lentiviral Vpr Interaction with the SLX4 Complex

Berger

Lawrence

Hué

et al. 2015

J Virol

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“…This restriction factor was identified based on studies showing that certain strains of lentiviruses that encode the auxiliary protein Vpx can bypass the block to viral replication in myeloid cells [21,32]. SAMHD1 was recovered in biochemical purification of Vpx and its associated cofactors and was identified as the restriction factor operating in myeloid cells [6,7].…”

Section: Samhd1 As An Exception?mentioning

confidence: 99%

How Samhd1 changes our view of viral restriction

Laguette¹,

Benkirane²

2012

Trends in Immunology

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Recent studies have uncovered sterile alpha motif and HD domain 1 (SAMHD1) as the restriction factor that blocks HIV-1 replication in myeloid cells. In contrast to previously identified HIV-1 restriction factors, SAMHD1 does not meet a countermeasure developed by HIV-1. However, HIV-2 and certain simian immunodeficiency virus (SIV) strains express the auxiliary protein Vpx that potently blocks SAMHD1. It is therefore perplexing why this function has been lost or not acquired during the course of lentiviral evolution. This article summarizes the similarities and differences between SAMHD1 and other HIV-1 restriction factors, while highlighting the new questions that are emerging about the crosstalk between restriction factors and innate immune responses. Intrinsic cellular defenses and the viral arsenalHIV was identified as a human pathogen 28 years ago [1]. As a result of the inability of the human host to mount a coordinated immune response to the virus, infection by HIV usually results in chronic activation of the immune system that paradoxically allows for poorly controlled viral replication and immune exhaustion: the hallmark of AIDS. HIV-1 has evolved from SIVcpz, which causes AIDS in its natural chimpanzee host, whereas HIV-2 has evolved from SIVsm, which replicates to high levels in its natural simian host without causing disease [2] (Box 1). Hence, it is possible to speculate that lentiviruses and their host immune systems undergo an evolutionary co-adaptation to establish an equilibrium that will permit efficient spread without killing the host. However, tolerance to the infection is a multifactorial process that requires a fertile ground in the host as much as specific features of the virus. Here, we review the recent advances related to how host restriction factors may influence immune sensing and response against HIV. In particular, we examine the recent identification that the immune modulator SAMHD1 is the HIV restriction factor operating in myeloid cells, which are key players in the immune response during viral infection. A not so fertile ground?Upon entry into the human host, viruses are confronted with numerous blocks that oppose their replication (Figure 1). The first line of defense to be triggered is the so-called 'intrinsic' immune system. The intrinsic immune system includes proteins that detect the presence of the assailant pattern recognition receptors (PRRs), [Box 2] and which initiate a subsequent immune response, as well as proteins referred to as restriction factors that are directly devoted to arresting the replication cycle of the virus. To date, four restriction factors have been identified that specifically block HIV-1 replication: tripartite motif (TRIM)5α, apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts (APOBEC3G) (A3G), bone marrow stromal cell antigen 2 (BST-2) (also known as tetherin) and SAMHD1 [3][4][5][6][7]. Host restriction factor characteristicsTRIM5α interacts with...

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“…Until recently most of the studies involving lentiviruses as tools to transfer genes into human DCs reported the use of Vpr/Vpxencoding SIV-derived or HIV-1-based vectors transcomplemented with Vpr/Vpx-encoding VLPs (8,40,42,43,51,59,74). Vpx is an accessory protein from SIV and HIV-2 viruses known to enable the inhibition of a host defense mechanism against infection, depending in part on the Cul4-based E3 ubiquitin ligase complex (40,43).…”

Section: Discussionmentioning

confidence: 99%

“…Vpx is an accessory protein from SIV and HIV-2 viruses known to enable the inhibition of a host defense mechanism against infection, depending in part on the Cul4-based E3 ubiquitin ligase complex (40,43). Vpx has been recently described as an interactant of the cellular host protein SAMHD1 identified as a major restriction factor of the transduction of myeloid cells by HIV-1-based viruses (47,54).…”

Section: Discussionmentioning

confidence: 99%

Measles Virus Glycoprotein-Pseudotyped Lentiviral Vectors Are Highly Superior to Vesicular Stomatitis Virus G Pseudotypes for Genetic Modification of Monocyte-Derived Dendritic Cells

Humbert

Frecha

Bouafia

et al. 2012

J Virol

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

Abstract: Human immunodeficiency virus type 2 (HIV-2)/simian immunodeficiency virus SIV SM Vpx is incorporated into virion particles and is thus

Cited by 121 publications

References 49 publications

G ₂ /M Cell Cycle Arrest Correlates with Primate Lentiviral Vpr Interaction with the SLX4 Complex

G ₂ /M Cell Cycle Arrest Correlates with Primate Lentiviral Vpr Interaction with the SLX4 Complex

How Samhd1 changes our view of viral restriction

Measles Virus Glycoprotein-Pseudotyped Lentiviral Vectors Are Highly Superior to Vesicular Stomatitis Virus G Pseudotypes for Genetic Modification of Monocyte-Derived Dendritic Cells

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

Abstract: Human immunodeficiency virus type 2 (HIV-2)/simian immunodeficiency virus SIV SM Vpx is incorporated into virion particles and is thus

Cited by 121 publications

References 49 publications

G 2 /M Cell Cycle Arrest Correlates with Primate Lentiviral Vpr Interaction with the SLX4 Complex

G 2 /M Cell Cycle Arrest Correlates with Primate Lentiviral Vpr Interaction with the SLX4 Complex

How Samhd1 changes our view of viral restriction

Measles Virus Glycoprotein-Pseudotyped Lentiviral Vectors Are Highly Superior to Vesicular Stomatitis Virus G Pseudotypes for Genetic Modification of Monocyte-Derived Dendritic Cells

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

G ₂ /M Cell Cycle Arrest Correlates with Primate Lentiviral Vpr Interaction with the SLX4 Complex

G ₂ /M Cell Cycle Arrest Correlates with Primate Lentiviral Vpr Interaction with the SLX4 Complex