Functional Interactions of Human Immunodeficiency Virus Type 1 Integrase with Human and Yeast HSP60

Parissi, Vincent; Calmels, Christina; Soultrait, Vaea Richard de; Caumont, Anne; Fournier, Michel; Chaignepain, Stéphane; Litvak, Simón

doi:10.1128/jvi.75.23.11344-11353.2001

Cited by 52 publications

(40 citation statements)

References 36 publications

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“…As IN is also an RT binding protein, the precise contacts between eEF1 subunits and RTC components requires further analysis. It is worth noting that eEF1A was shown to interact with HIV-1 IN in vitro (20,21), which may be relevant to coimmunoprecipitations of IN with eEF1A or eEF1G observed in this study. Given a tight association between RT and IN (22), it is possible that an IN and eEF1A interaction resulted in coprecipitation of the RT p51 subunit.…”

Section: Discussionmentioning

confidence: 99%

Eukaryotic elongation factor 1 complex subunits are critical HIV-1 reverse transcription cofactors

Warren

Wei

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Cellular proteins have been implicated as important for HIV-1 reverse transcription, but whether any are reverse transcription complex (RTC) cofactors or affect reverse transcription indirectly is unclear. Here we used protein fractionation combined with an endogenous reverse transcription assay to identify cellular proteins that stimulated late steps of reverse transcription in vitro. We identified 25 cellular proteins in an active protein fraction, and here we show that the eEF1A and eEF1G subunits of eukaryotic elongation factor 1 (eEF1) are important components of the HIV-1 RTC. eEF1A and eEF1G were identified in fractionated human T-cell lysates as reverse transcription cofactors, as their removal ablated the ability of active protein fractions to stimulate late reverse transcription in vitro. We observed that the p51 subunit of reverse transcriptase and integrase, two subunits of the RTC, coimmunoprecipitated with eEF1A and eEF1G. Moreover eEF1A and eEF1G associated with purified RTCs and colocalized with reverse transcriptase following infection of cells. Reverse transcription in cells was sharply down-regulated when eEF1A or eEF1G levels were reduced by siRNA treatment as a result of reduced levels of RTCs in treated cells. The combined evidence indicates that these eEF1 subunits are critical RTC stability cofactors required for efficient completion of reverse transcription. The identification of eEF1 subunits as unique RTC components provides a basis for further investigations of reverse transcription and trafficking of the RTC to the nucleus. purification | mass spectrometry | cellular factor | siRNA knock down | virus replication T he HIV type-1 (HIV-1) reverse transcriptase (RT) enzyme carries out reverse transcription through DNA polymerase and RNase H activities, which mediate a sequential series of steps that include the initiation of DNA synthesis producing negative strand strong stop DNA (−ssDNA), full-length negative-strand DNA, positive-strand DNA, and intact preintegrative doublestrand DNA (reviewed elsewhere 1). The ability of HIV-1 to efficiently produce early reverse transcription products in vitro has been described (2). However, under in vitro conditions, the production of late reverse transcription products is less efficient than that observed in HIV-1-infected cells (3, 4), suggesting that host cellular factors are required. After entry into the host cell cytoplasm, the HIV-1 core, containing the viral genomic RNA, RT, and integrase (IN), reorganizes to form the reverse transcription complex (RTC). The RTC requires both IN and RT to be active (5), and they are believed to recruit cellular factors to facilitate DNA synthesis (6). Although two-hybrid library and genomewide RNAi screening methods have implicated more than 50 cellular proteins as important for reverse transcription (6, 7), whether any of these cellular proteins are RTC components, or whether they direct the RTC in other ways, is unclear.Attempts to purify and to identify cellular RTC cofactors by more conventional methods ...

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Section: Discussionmentioning

confidence: 99%

Eukaryotic elongation factor 1 complex subunits are critical HIV-1 reverse transcription cofactors

Warren

Wei

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…LEDGF/p75 (0.2 M) was present in lane 4. Full-length GST-LEDGF/p75 (lanes 5-8), GST-LEDGF-(1-325) (lanes 9-11) or GST-LEDGF-(326 -530) (lanes [12][13][14] were added at the indicated concentrations. D, LEDGF-(347-471) (lanes 5-7) or GST (lane 9) were added together with full-length protein as competitors at the indicated concentrations.…”

Section: Tr2 Is the Functional Ledgf/p75 Ibd-to Identify Region(s) Ofmentioning

confidence: 99%

“…10). Furthermore, several proteins were reported to directly interact with HIV-1 IN, including viral reverse transcriptase (9), a component of the SWI-SNF chromatin-remodeling complex INI1 (11), uracil DNA glycosylase UNG2 (12), heat shock protein HSP60 (13), a DNA repair protein Rad18 (14), a Polycomb group protein EED (15) and lens epithelium-derived growth factor/transcriptional coactivator p75 (LEDGF/p75) (Ref. 16, for a review see Ref.…”

mentioning

confidence: 99%

Identification of an Evolutionarily Conserved Domain in Human Lens Epithelium-derived Growth Factor/Transcriptional Co-activator p75 (LEDGF/p75) That Binds HIV-1 Integrase

Cherepanov¹,

Devroe

Silver

et al. 2004

Journal of Biological Chemistry

253

337

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“…To identify cellular factors that participate in or interfere with viral integration, cellular proteins interacting with IN have been screened for and characterized (18)(19)(20)(21)(22). In particular, the transcriptional coactivator lens epithelium-derived growth factor/ transcription coactivator p75 (LEDGF/p75) has been reported to tether IN to chromosomes (23,24) and to contribute to the targeting of viral DNA to preferential integration sites (25).…”

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confidence: 99%

von Hippel–Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step

Mousnier

Kubat

Massias-Simon

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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HIV-1 integrase, the viral enzyme responsible for provirus integration into the host genome, can be actively degraded by the ubiquitin-proteasome pathway. Here, we identify von HippelLindau binding protein 1(VBP1), a subunit of the prefoldin chaperone, as an integrase cellular binding protein that bridges interaction between integrase and the cullin2 (Cul2)-based von Hippel-Lindau (VHL) ubiquitin ligase. We demonstrate that VBP1 and Cul2/VHL are required for proper HIV-1 expression at a step between integrase-dependent proviral integration into the host genome and transcription of viral genes. Using both an siRNA approach and Cul2/VHL mutant cells, we show that VBP1 and the Cul2/VHL ligase cooperate in the efficient polyubiquitylation of integrase and its subsequent proteasome-mediated degradation. Results presented here support a role for integrase degradation by the prefoldin-VHL-proteasome pathway in the integrationtranscription transition of the viral replication cycle.prefoldin ͉ ubiquitin ͉ VHL ͉ retrovirus ͉ transcription

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Functional Interactions of Human Immunodeficiency Virus Type 1 Integrase with Human and Yeast HSP60

Cited by 52 publications

References 36 publications

Eukaryotic elongation factor 1 complex subunits are critical HIV-1 reverse transcription cofactors

Eukaryotic elongation factor 1 complex subunits are critical HIV-1 reverse transcription cofactors

Identification of an Evolutionarily Conserved Domain in Human Lens Epithelium-derived Growth Factor/Transcriptional Co-activator p75 (LEDGF/p75) That Binds HIV-1 Integrase

von Hippel–Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step

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