Abstract:
:Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 genome encodes the Tax protein that plays essential regulatory roles in HTLV-1 replication and oncogenic transformation of T lymphocytes. Despite intensive study of Tax, how Tax interfaces with host signaling pathways to regulate virus replication and drive T-cell proliferation and immortalization remains poorly understood. To gain new insight into the mechanisms of Tax function and regulation, we used tandem affinity purification and mass spectrometry to identify novel cellular Tax-interacting proteins. This screen identified heat shock protein 90 (HSP90) as a new binding partner of Tax. The interaction between HSP90 and Tax was validated by coimmunoprecipitation assays, and colocalization between the two proteins was observed by confocal microscopy. Treatment of HTLV-1-transformed cells with the HSP90 inhibitor 17-DMAG elicited proteasomal degradation of Tax in the nuclear matrix with concomitant inhibition of NF-κB and HTLV-1 long terminal repeat (LTR) activation. Knockdown of HSP90 by lentiviral shRNAs similarly provoked a loss of Tax protein in HTLV-1-transformed cells. Finally, treatment of HTLV-1-transformed cell lines with 17-DMAG suppressed HTLV-1 replication and promoted apoptotic cell death. Taken together, our results reveal that Tax is a novel HSP90 client protein and HSP90 inhibitors may exert therapeutic benefits for ATL and HAM/TSP patients.
journal_name
J Viroljournal_title
Journal of virologyauthors
Gao L,Harhaj EWdoi
10.1128/JVI.02006-13subject
Has Abstractpub_date
2013-12-01 00:00:00pages
13640-54issue
24eissn
0022-538Xissn
1098-5514pii
JVI.02006-13journal_volume
87pub_type
杂志文章abstract::Epstein-Barr virus (EBV) in vivo is known to establish persistent infection in resting, circulating memory B cells and to productively replicate in plasma cells. Until now, the molecular mechanism of how EBV switches from latency to lytic replication in vivo was not known. Here, we report that the plasma cell differen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01055-07
更新日期:2007-12-01 00:00:00
abstract::The parameters governing the activity of the cloned T4 gene 23, which codes for the major T4 head protein, were analyzed. Suppressor-negative bacteria carrying wild-type T4 gene 23 cloned into plasmid pCR1 or pBR322 were infected with T4 gene 23 amber phage also carrying mutations in the following genes: (i) denA and ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.1.46-59.1981
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pub_type: 杂志文章
doi:10.1128/jvi.74.23.10958-10964.2000
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abstract::The nef gene contributes to the replication of primate lentiviruses by altering the trafficking of cellular proteins involved in adaptive immunity (class I and II major histocompatibility complex [MHC]) and viral transmission (CD4 and DC-SIGN). A conserved acidic leucine-based sequence (E(160)xxxLL) within human immun...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.4.1837-1849.2006
更新日期:2006-02-01 00:00:00
abstract::Immunity to human immunodeficiency virus virion-like structures or a polyprotein has been examined after DNA immunization with Rev-independent expression vectors. A Gag-Pol fusion protein stimulated cytotoxic T lymphocyte and antibody responses to Gag and Pol, while a Gag-Pol pseudoparticle did not elicit substantial ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.10.4947-4951.2001
更新日期:2001-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.9.4115-4122.1990
更新日期:1990-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00835-06
更新日期:2006-10-01 00:00:00
abstract::Hepatitis E virus (HEV), a positive-strand RNA virus, is an important causative agent of waterborne hepatitis. Expression of cDNA (encoding amino acids 1 to 979 of HEV nonstructural open reading frame 1) in insect cells resulted in synthesis of a 110-kDa protein (P110), a fraction of which was proteolytically processe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.14.6249-6255.2001
更新日期:2001-07-01 00:00:00
abstract::Three serial passage series of simian virus 40 (SV40) in CV-1 cells were initiated by infection directly from the same wild-type plaque isolate, three series were initiated by infection with another plaque isolate, and two series were initiated with each of two other plaque isolates. Aberrant SV40 genomes were not det...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.42.2.730-733.1982
更新日期:1982-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01985-12
更新日期:2013-02-01 00:00:00
abstract:UNLABELLED:The structure of adenovirus outer capsid was revealed recently at 3- to 4-Å resolution (V. Reddy, S. Natchiar, P. Stewart, and G. Nemerow, Science 329:1071-1075, 2010, http://dx.doi.org/10.1126/science.1187292); however, precise details on the function and biochemical and structural features for the inner co...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00935-14
更新日期:2014-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00968-06
更新日期:2007-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02040-09
更新日期:2010-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02692-10
更新日期:2011-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.4.1818-1821.1989
更新日期:1989-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.2.519-528.1981
更新日期:1981-08-01 00:00:00
abstract::Varicella-zoster virus (VZV) causes varicella and establishes latency in sensory nerve ganglia, but the characteristics of VZV latency are not well defined. Immunohistochemical detection of the VZV immediate-early 63 (IE63) protein in ganglion neurons has been described, but there are significant discrepancies in esti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02416-09
更新日期:2010-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.3.944-948.1985
更新日期:1985-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.4.2052-2056.2000
更新日期:2000-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.6.5156-5161.1999
更新日期:1999-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.2.757-766.1990
更新日期:1990-02-01 00:00:00
abstract::Studies of rotavirus morphogenesis, transport, and release have shown that although these viruses are released from the apical surface of polarized intestinal cells before cellular lysis, they do not follow the classic exocytic pathway. Furthermore, increasing evidence suggests that lipid rafts actively participate in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.8.3935-3946.2006
更新日期:2006-04-01 00:00:00
abstract::Primary sympathetic neuronal cultures were maintained for up to 5 weeks after inoculation with herpes simplex virus (HSV) without evidence of viral infection. Upon deprivation of nerve growth factor, the cultures produced infectious HSV, indicating that the cultures harbored latent HSV. This study demonstrates a funct...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.7.2311-2315.1987
更新日期:1987-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.20.2.465-477.1976
更新日期:1976-11-01 00:00:00
abstract::Transcription and replication signals within the negative-sense genomic RNA of vesicular stomatitis virus (VSV) are located at the 3' terminus. To identify these signals, we have used a transcription- and replication-competent minigenome of VSV to generate a series of deletions spanning the first 47 nucleotides at the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.1.444-452.1999
更新日期:1999-01-01 00:00:00
abstract::Plasma human immunodeficiency virus type 1 (HIV-1) turnover and kinetics were studied in children aged 15 days to 2 years following the initiation of a triple antiretroviral drug regimen consisting of zidovudine, lamivudine, and nevirapine. HIV-1 turnover was at least as rapid as that previously described in adults; t...
journal_title:Journal of virology
pub_type: 临床试验,杂志文章
doi:10.1128/JVI.73.1.362-367.1999
更新日期:1999-01-01 00:00:00
abstract::Previous studies using wild-type Encephalomyocarditis virus (EMCV) and Mengo virus, which have long poly(C) tracts (61 to 146 C's) at the 5' nontranslated region of the genome, and variants of these viruses genetically engineered to truncate or substitute the poly(C) tracts have produced conflicting data on the role o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.17.9136-9146.2003
更新日期:2003-09-01 00:00:00
abstract::Rotavirus replication and virulence are strongly influenced by virus strain and host species. The rotavirus proteins VP3, VP4, VP7, NSP1, and NSP4 have all been implicated in strain and species restriction of replication; however, the mechanisms have not been fully determined. Simian (RRV) and bovine (UK) rotaviruses ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02408-10
更新日期:2011-03-01 00:00:00
abstract::The inhibition of multilineage hematopoiesis which occurs in the severe combined immunodeficiency mouse with transplanted human fetal thymus and liver tissues (SCID-hu Thy/Liv) due to human immunodeficiency virus type 1 (HIV-1) infection is also accompanied by a severe loss of c-Mpl expression on these progenitor cell...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.20.11385-11392.2004
更新日期:2004-10-01 00:00:00
abstract::RNA viruses of filamentous fungi fall into two broad categories, those that contain double-stranded RNA (dsRNA) genomes in rigid particles and those that are more closely related to positive-sense, single-stranded RNA viruses with dsRNA replicative intermediates found within lipid vesicles. Effective infectivity syste...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.2.892-898.2004
更新日期:2004-01-01 00:00:00