Human immunodeficiency virus-1 Nef suppresses Hsp70-mediated Tat activation

Sugiyama, Ryuichi; Naganuma, Haruki; Nishitsuji, Hironori; Takaku, Hiroshi

doi:10.1016/j.febslet.2011.09.029

Cited by 16 publications

(22 citation statements)

References 33 publications

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“…Moreover, Hsp70 proteins mediate Tat activation and viral transcription, and are released in HIV-1 virions (48–50). Both PSF and NONO bind the HIV-1 RNA instability element (INS), but only PSF causes a down-regulation of the Rev-dependent gag and env transcripts (51).…”

Section: Discussionmentioning

confidence: 99%

ADAR1 restricts LINE-1 retrotransposition

et al. 2016

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Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosines to inosines in double-stranded RNAs. ADAR1 was demonstrated to be functional on different viruses exerting either antiviral or proviral effects. Concerning HIV-1, several studies showed that ADAR1 favors viral replication. The aim of this study was to investigate the composition of the ADAR1 ribonucleoprotein complex during HIV-1 expression. By using a dual-tag affinity purification procedure in cells expressing HIV-1 followed by mass spectrometry analysis, we identified 14 non-ribosomal ADAR1-interacting proteins, most of which are novel. A significant fraction of these proteins were previously demonstrated to be associated to the Long INterspersed Element 1 (LINE1 or L1) ribonucleoparticles and to regulate the life cycle of L1 retrotransposons that continuously re-enter host-genome.Hence, we investigated the function of ADAR1 in the regulation of L1 activity.By using different cell-culture based retrotransposition assays in HeLa cells, we demonstrated a novel function of ADAR1 as suppressor of L1 retrotransposition. Apparently, this inhibitory mechanism does not occur through ADAR1 editing activity. Furthermore, we showed that ADAR1 binds the basal L1 RNP complex. Overall, these data support the role of ADAR1 as regulator of L1 life cycle.

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Section: Discussionmentioning

confidence: 99%

ADAR1 restricts LINE-1 retrotransposition

et al. 2016

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“…It is recently reported that Nef degrades Tat protein by the UPS (Sugiyama et al, 2011), which is crucial for an efficient virus replication, and counteracts the tetherin protein in SIVs, whose genomes lack vpu (Jia et al, 2009; Sauter et al, 2009; Serra-Moreno et al, 2013; Zhang et al, 2009). Further, it is reported that K144 in HIV-1 Nef is di-ubiquitinated for downregulation of CD4 and MHC-I (Cai et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Function of ubiquitin (Ub) specific protease 15 (USP15) in HIV-1 replication and viral protein degradation

et al. 2016

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HIV-1 Nef is necessary and may be sufficient for HIV-1-associated AIDS pathogenicity, in that knockout of Nef alone can protect HIV-infected patients from AIDS. We therefore investigated the feasibility of physical knockout of Nef, using the host ubiquitin proteasome system in HIV-1-infected cells. Our co-immunoprecipitation analysis demonstrated that Nef interacted with ubiquitin specific protease 15 (USP15), and that USP15, which is known to stabilize cellular proteins, degraded Nef. Nef could also cause decay of USP15, although Nef-mediated degradation of USP15 was weaker than USP15-mediated Nef degradation. Direct interaction between Nef and USP15 was essential for the observed reciprocal decay of the proteins. Further, USP15 degraded not only Nef but also HIV-1 structural protein, Gag, thereby substantially inhibiting HIV-1 replication. However, Gag did not degrade USP15, indicating that the Nef and USP15 complex, in distinction to other viral proteins, play an integral role in coordinating viral protein degradation and hence HIV-1 replication. Moreover, Nef and USP15 globally suppressed ubiquitylation of cellular proteins, indicating that these proteins are major determinants for the stability of cellular as well as viral proteins. Taken together, these data indicate that Nef and USP15 are vital in regulating degradation of viral and cellular proteins and thus HIV-1 replication, and specific degradation of viral, not cellular proteins, by USP15 points to USP15 as a candidate therapeutic agent to combat AIDS by eliminating viral proteins from the infected cells via USP15-mediated proteosomal degradation.

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“…siRNA knockdown of Hsp70 resulted in activation of caspase-9 and caspase-3 (Behnsawy et al, 2011). Hsp70 has been shown during infection to modulate viral entry, transcription, translation, nuclear entry, and viron release (Halder et al, 2011; Sugiyama et al, 2011). A very recent study questioned the previous suggestion and indicated that Hsp70 may not have an IRES within its 5′ UTR (Sun et al, 2011).…”

Section: Cellular Ires-containing Genes and Their Roles In Er Stress mentioning

confidence: 99%

IRES-Dependent Translational Control during Virus-Induced Endoplasmic Reticulum Stress and Apoptosis

et al. 2012

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Many virus infections and stresses can induce endoplasmic reticulum (ER) stress response, a host self-defense mechanism against viral invasion and stress. During this event, viral and cellular gene expression is actively regulated and often encounters a switching of the translation initiation from cap-dependent to internal ribosome-entry sites (IRES)-dependent. This switching is largely dependent on the mRNA structure of the 5′ untranslated region (5′ UTR) and on the particular stress stimuli. Picornaviruses and some other viruses contain IRESs within their 5′ UTR of viral genome and employ an IRES-driven mechanism for translation initiation. Recently, a growing number of cellular genes involved in growth control, cell cycle progression and apoptosis were also found to contain one or more IRES within their long highly structured 5′ UTRs. These genes initiate translation usually by a cap-dependent mechanism under normal physiological conditions; however, in certain environments, such as infection, starvation, and heat shock they shift translation initiation to an IRES-dependent modality. Although the molecular mechanism is not entirely understood, a number of studies have revealed that several cellular biochemical processes are responsible for the switching of translation initiation to IRES-dependent. These include the cleavage of translation initiation factors by viral and/or host proteases, phosphorylation (inactivation) of host factors for translation initiation, overproduction of homologous proteins of cap-binding protein eukaryotic initiation factors (eIF)4E, suppression of cap-binding protein eIF4E expression by specific microRNA, activation of enzymes for mRNA decapping, as well as others. Here, we summarize the recent advances in our understanding of the molecular mechanisms for the switching of translation initiation, particularly for the proteins involved in cell survival and apoptosis in the ER stress pathways during viral infections.

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Human immunodeficiency virus-1 Nef suppresses Hsp70-mediated Tat activation

Abstract: Hsp70 physically interacts with Tat by anti tag coimmunoprecipitation (View interaction)

Cited by 16 publications

References 33 publications

ADAR1 restricts LINE-1 retrotransposition

ADAR1 restricts LINE-1 retrotransposition

Function of ubiquitin (Ub) specific protease 15 (USP15) in HIV-1 replication and viral protein degradation

IRES-Dependent Translational Control during Virus-Induced Endoplasmic Reticulum Stress and Apoptosis

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