Caught in translation: innate restriction of HIV mRNA translation by a schlafen family protein

Jakobsen, Martin R.; Mogensen, Trine H.; Paludan, Søren R.

doi:10.1038/cr.2012.155

Cited by 22 publications

(18 citation statements)

References 12 publications

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“…Thus, HIV-infected macrophages do not produce significant amounts of type I IFN, ISGs, or proinflammatory cytokines but instead evade recognition by the immune system allowing them to serve as a viral reservoir. Despite this, a subset of ISGs is now known to restrict HIV replication, hence suggesting that some innate signaling is activated and potentially targeted by the virus in macrophages [48, 49]. More in-depth understanding of the molecular mechanisms behind the HIV-macrophage interactions may provide insight into the pathogenesis of immune dysfunction and development of immunodeficiency during HIV infection.…”

Section: Discussionmentioning

confidence: 99%

Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages

Diget

Zuwała

Berg

et al. 2013

Mediators of Inflammation

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Macrophages play an important role in human immunodeficiency virus (HIV) pathogenesis and contribute to establishment of a viral reservoir responsible for continuous virus production and virus transmission to T cells. In this study, we investigated the differences between various monocyte-derived macrophages (MDMs) generated through different differentiation protocols and evaluated different cellular, immunological, and virological properties. We found that elevated and persistent HIV-1 pWT/BaL replication could be obtained only in MDMs grown in RPMI containing macrophage colony-stimulating factor (M-CSF). Interestingly, this MDM type was also most responsive to toll-like receptor stimulation. By contrast, all MDM types were activated to a comparable extent by intracellular DNA, and the macrophage serum-free medium-(Mac-SFM-)differentiated MDMs responded strongly to membrane fusion through expression of CXCL10. Finally, we found that HIV infection of RPMI/M-CSF-differentiated MDMs induced low-grade expression of two interferon-stimulated genes in some donors. In conclusion, our study demonstrates that the differentiation protocol used greatly influences the ability of MDMs to activate innate immune reactions and support HIV-1 replication. Paradoxically, the data show that the MDMs with the strongest innate immune response were also the most permissive for HIV-1 replication.

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Section: Discussionmentioning

confidence: 99%

Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages

Diget

Zuwała

Berg

et al. 2013

Mediators of Inflammation

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“…On the other hand, multiple HIV-1 restriction factors inhibiting specific steps in the late phase of HIV-1 replication have already been described. The list includes the recently identified HIV-1 restriction factor Schlafen 11 that interferes with late steps of the HIV-1 life cycle by reducing the expression of viral proteins in a codon-usage-dependent manner 73,74 . Acting more directly on the release step, 2′,3′-cyclic-nucleotide 3′-phosphodiesterase reduces the assembly and budding of infectious HIV-1 in some cell types 75 .…”

Section: Block To the Late Phase Of Hiv-1 Replication In Resting Cd4+mentioning

confidence: 99%

Restrictions to HIV-1 replication in resting CD4+ T lymphocytes

et al. 2013

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CD4+ T lymphocytes represent the main target cell population of human immunodeficiency virus (HIV). In an activated state, CD4+ T cells residing in lymphoid organs are a major reservoir of ongoing HIV-1 replication in infected individuals. In contrast, resting CD4+ T cells are highly resistant to productive HIV-1 infection, yet are massively depleted during disease progression and represent a substantial latent reservoir for the virus in vivo. Barriers preventing replication of HIV-1 in resting CD4+ T cells include a rigid layer of cortical actin and, early after HIV-1 entry, a block that limits reverse transcription of incoming viral RNA genomes. Defining the molecular bases of these restrictions has remained one of the central open questions in HIV research. Recent advances unraveled mechanisms by which HIV-1 bypasses the entry block and established the host cell restriction factor SAMHD1, a deoxynucleoside triphosphate triphosphohydrolase, as a central determinant of the cellular restriction to HIV-1 reverse transcription in resting CD4+ T cells. This review summarizes our current molecular and pathophysiological understanding of the multi-faceted interactions of HIV-1 with resting CD4+ T lymphocytes.

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“…Currently known host restriction factors consist of five major classes that are the DNA deaminase subfamily APOBEC3 (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like) [1][2][3], the Ubl conjugation ligase TRIM5α (Tripartite motif-containing protein 5 alpha) [4][5][6], the integral membrane protein BST-2 (bone stromal tumor protein 2)/tetherin [7,8], the dNTP hydrolase and RNase SAMHD1 (SAM domain and HD domain-containing protein 1) [9][10][11][12][13], and the tRNA binding protein SLFN11 (Schlafen 11) [14][15][16]. The APOBEC3 (A3) family includes seven members (A3A to A3D and A3F to A3H) that are located in a gene cluster on chromosome 22 [17][18][19], from which A3D, A3F, A3G and A3H have HIV-1 restrictive capacities [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

A functional conserved intronic G run in HIV-1 intron 3 is critical to counteract APOBEC3G-mediated host restriction

et al. 2014

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Caught in translation: innate restriction of HIV mRNA translation by a schlafen family protein

Cited by 22 publications

References 12 publications

Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages

Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages

Restrictions to HIV-1 replication in resting CD4+ T lymphocytes

A functional conserved intronic G run in HIV-1 intron 3 is critical to counteract APOBEC3G-mediated host restriction

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