Automated Genome-Wide Visual Profiling of Cellular Proteins Involved in HIV Infection

Genovesio, Auguste; Kwon, Yong-Jun; Windisch, Marc P.; Kim, Nam Youl; Choi, Seo Yeon; Kim, Hi Chul; Jung, Sungyong; Mammano, Fabrizio; Perrin, Virginie; Boese, Annette; Casartelli, Nicoletta; Schwartz, Olivier; Nehrbass, Ulf; Emans, Neil

doi:10.1177/1087057111415521

Cited by 47 publications

(37 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although a role for RNase H2 in the metabolism of endogenous retroelements has not been determined, the RNase H2 complex does act on RNA-DNA hybrids -nucleic acid substrates that are generated transiently during reverse transcription. Of note, RNase H2 has been reported to facilitate HIV replication by a currently unknown mechanism 62 . ADAR, similar to TREX1 and SAMHD1, is an IFN-stimulated protein and it can edit the SINEs known as Alu retroelements, which constitute approximately 10% of the human genome.…”

Section: Retroelements and Dna Damage In Agsmentioning

confidence: 99%

Aicardi–Goutières syndrome and the type I interferonopathies

2015

View full text Add to dashboard Cite

Dissection of the genetic basis of Aicardi-Goutières syndrome has highlighted a fundamental link between nucleic acid metabolism, innate immune sensors and type I interferon induction. This had led to the concept of the human interferonopathies as a broader set of Mendelian disorders in which a constitutive upregulation of type I interferon activity directly relates to disease pathology. Here, we discuss the molecular and cellular basis of the interferonopathies, their categorization, future treatment strategies and the insights they provide into normal physiology.

show abstract

Section: Retroelements and Dna Damage In Agsmentioning

confidence: 99%

Aicardi–Goutières syndrome and the type I interferonopathies

2015

View full text Add to dashboard Cite

show abstract

“…In HIV-1-infected cells, TREX1 degrades nonproductive transcripts to clear excess viral cDNA, preventing innate immune activation (27,28). The RNase H2 recognizes and cleaves ribonucleotides present in RNA/DNA duplexes (29,30), and silencing RNASEH2A impairs HIV replication (31). This suggests a role in HIV infection.…”

mentioning

confidence: 99%

Aicardi-Goutières Syndrome Gene and HIV-1 Restriction Factor SAMHD1 Is a dGTP-regulated Deoxynucleotide Triphosphohydrolase

Powell¹,

Holland²,

Hollis

et al. 2011

Journal of Biological Chemistry

313

310

View full text Add to dashboard Cite

“…. Further work is required to decipher the mechanism by which SAMHD1 mediates its restriction activity.In contrast to SAMHD1 degradation, TREX1 and RN-ase H2 deficiencies have a deleterious effect on HIV-1 replication [53]. For example, TREX1 is part of the reticulum-associated DNase complex SET, which inhibits auto-integration of the viral genome after completion of reverse transcription [54] and causes the degradation of abortive reverse transcription products, thereby avoiding accumulation of these DNA products and subsequent recognition by TLRs [55].…”

mentioning

confidence: 99%

How Samhd1 changes our view of viral restriction

Laguette¹,

Benkirane²

2012

Trends in Immunology

View full text Add to dashboard Cite

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...

show abstract

Automated Genome-Wide Visual Profiling of Cellular Proteins Involved in HIV Infection

Cited by 47 publications

References 23 publications

Aicardi–Goutières syndrome and the type I interferonopathies

Aicardi–Goutières syndrome and the type I interferonopathies

Aicardi-Goutières Syndrome Gene and HIV-1 Restriction Factor SAMHD1 Is a dGTP-regulated Deoxynucleotide Triphosphohydrolase

How Samhd1 changes our view of viral restriction

Contact Info

Product

Resources

About