Abstract:
:The activity of phosphatidylinositol 4-kinase class III beta (PI4KIIIβ) has been shown to be required for the replication of multiple picornaviruses; however, it is unclear whether a physical association between PI4KIIIβ and the viral replication machinery exists and, if it does, whether association is necessary. We examined the ability of the 3A protein from 18 different picornaviruses to form a complex with PI4KIIIβ by affinity purification of Strep-Tagged transiently transfected constructs followed by mass spectrometry and Western blotting for putative interacting targets. We found that the 3A proteins of Aichi virus, bovine kobuvirus, poliovirus, coxsackievirus B3, and human rhinovirus 14 all copurify with PI4KIIIβ. Furthermore, we found that multiple picornavirus 3A proteins copurify with the Golgi adaptor protein acyl coenzyme A (acyl-CoA) binding domain protein 3 (ACBD3/GPC60), including those from Aichi virus, bovine kobuvirus, human rhinovirus 14, poliovirus, and coxsackievirus B2, B3, and B5. Affinity purification of ACBD3 confirmed interaction with multiple picornaviral 3A proteins and revealed the ability to bind PI4KIIIβ in the absence of 3A. Mass-spectrometric analysis of transiently expressed Aichi virus, bovine kobuvirus, and human klassevirus 3A proteins demonstrated that the N-terminal glycines of these 3A proteins are myristoylated. Alanine-scanning mutagenesis along the entire length of Aichi virus 3A followed by transient expression and affinity purification revealed that copurification of PI4KIIIβ could be eliminated by mutation of specific residues, with little or no effect on recruitment of ACBD3. One mutation at the N terminus, I5A, significantly reduced copurification of both ACBD3 and PI4KIIIβ. The dependence of Aichi virus replication on the activity of PI4KIIIβ was confirmed by both chemical and genetic inhibition. Knockdown of ACBD3 by small interfering RNA (siRNA) also prevented replication of both Aichi virus and poliovirus. Point mutations in 3A that eliminate PI4KIIIβ association sensitized Aichi virus to PIK93, suggesting that disruption of the 3A/ACBD3/PI4KIIIβ complex may represent a novel target for therapeutic intervention that would be complementary to the inhibition of the kinase activity itself.
journal_name
J Viroljournal_title
Journal of virologyauthors
Greninger AL,Knudsen GM,Betegon M,Burlingame AL,Derisi JLdoi
10.1128/JVI.06778-11subject
Has Abstractpub_date
2012-04-01 00:00:00pages
3605-16issue
7eissn
0022-538Xissn
1098-5514pii
JVI.06778-11journal_volume
86pub_type
杂志文章abstract::The retroviral Gag precursor plays an important role in the assembly of virion particles. The capsid (CA) protein of the Gag molecule makes a major contribution to this process. In the crystal structure of the free CA protein of the human immunodeficiency virus type 1 (HIV-1), 11 residues of the C terminus were found ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.18.9675-9688.2004
更新日期:2004-09-01 00:00:00
abstract::Novel molecular approaches to inhibit human immunodeficiency virus type 1 (HIV-1) infection have received increasing attention because of the lack of effective antiviral drug therapies in vivo. We now demonstrate that cells can be intracellularly immunized by cytoplasmic expression of single-chain variable antibody fr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.6.3392-3400.1996
更新日期:1996-06-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) V3 loop is essential for coreceptor binding and principally determines tropism for the CCR5 and CXCR4 coreceptors. Using the dual-tropic virus HIV-1(R3A), we previously made an extensive panel of V3 deletions and identified subdomains within V3 that could differentially ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01751-08
更新日期:2009-04-01 00:00:00
abstract::Reciprocal three-factor crosses and the use of a partial revertant of a putative ribonucleotide reductase mutant of Escherichia coli B/5 as indicator have made it possible to map denA (deficient in endonuclease II) between nrd-11 (ribonucleotide reductase gene B) and amM69 (gene 63) on the bacteriophage T4 chromosome....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.1.184-186.1972
更新日期:1972-01-01 00:00:00
abstract::Human cytomegalovirus (HCMV) encodes several proteins that inhibit major histocompatibility complex (MHC) class I-dependent antigen presentation. The HCMV products US2 and US11 are each sufficient for causing the dislocation of human and murine MHC class I heavy chains from the lumen of the endoplasmic reticulum to th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.10.5043-5050.2002
更新日期:2002-05-01 00:00:00
abstract::Here we report the complete genome sequence of a dengue virus serotype 2 (DENV-2) strain, GZ40, isolated in Guangdong, China, in 2010. A phylogenetic analysis classified GZ40 into the Cosmopolitan genotype, while previous Chinese DENV-2 isolates belong to the Asian I genotype. The reemergence of the Cosmopolitan genot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02562-12
更新日期:2012-12-01 00:00:00
abstract::Poliovirus proteins, except P3-7c, are associated with the endoplasmic reticulum after extraction of the cytoplasm and centrifugation of membranes to equilibrium in sucrose gradients. Proteins P3-2, P2-X, and P3-9 are found preferentially among the rough endoplasmic reticulum, whereas P3-7c is located in smooth endopl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.52.3.777-783.1984
更新日期:1984-12-01 00:00:00
abstract::YY1 is a zinc finger transcription factor which acts as either a repressor or an activator dependent on the promoter context. YY1 is a potent activator of the genuine human papillomavirus type 18 (HPV-18) upstream regulatory region (URR) in HeLa cells, which are known for high-level expression of the HPV-18 early gene...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.1.1-12.1995
更新日期:1995-01-01 00:00:00
abstract::Human cytomegalovirus (CMV) is the leading cause of prenatal viral infection. Affected infants may suffer intrauterine growth retardation and serious neurologic impairment. Analysis of spontaneously aborted conceptuses shows that CMV infects the placenta before the embryo or fetus. In the human hemochorial placenta, m...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.15.6808-6820.2000
更新日期:2000-08-01 00:00:00
abstract::The major immediate-early (MIE) transactivator proteins of cytomegaloviruses (CMV) play a pivotal role in the initiation of virus-host cell interactions. Therefore, cis- and trans-acting factors influencing the expression of these proteins through their upstream promoter-enhancer regions are important determinants of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.1.516-529.1993
更新日期:1993-01-01 00:00:00
abstract::Incorporation of the vaccinia virus A36R protein into the outer membrane of intracellular enveloped virions (IEV) is dependent on expression of the A33R protein. Possible interactions of the 200-amino-acid cytoplasmic domain of the A36R protein with itself or with the cytoplasmic domain of the A33R, A34R, B5R, or F12L...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.7.4113-4126.2003
更新日期:2003-04-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) infection of CD4-positive lymphocytes is accompanied by acute cytopathic effects, i.e., syncytium formation and single-cell lysis. Syncytium formation involves cell-cell fusion mediated by viral envelope glycoproteins on the surface of infected cells and by CD4 glycoproteins...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.3.1340-1354.1996
更新日期:1996-03-01 00:00:00
abstract::The N-terminal alpha-helix domain of the human immunodeficiency virus type 1 (HIV-1) Nef protein plays important roles in enhancement of viral infectivity, virion incorporation of Nef, and the down-regulation of major histocompatibility complex class I (MHC-I) expression on cell surfaces. In this study, we demonstrate...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.6.2907-2912.2000
更新日期:2000-03-01 00:00:00
abstract::Sequencing and reversion analysis of murine hepatitis virus (MHV) temperature-sensitive (ts) viruses has identified putative ts mutations in the replicase nonstructural proteins (nsp's) of these coronaviruses. In this study, reverse transcriptase PCR sequencing of the RNA genome of an isolate of the MHV ts virus Alb t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00203-08
更新日期:2008-06-01 00:00:00
abstract::High-risk human papillomaviruses (HPVs) are the causative agents of certain human cancers. HPV type 16 (HPV16) is the papillomavirus most frequently associated with cervical cancer in women. The E6 and E7 genes of HPV are expressed in cells derived from these cancers and can transform cells in tissue culture. Animal e...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.7.5887-5893.1999
更新日期:1999-07-01 00:00:00
abstract::Densonucleosis viruses 1 and 2 both contain the three polyamines putrescine, spermidine, and spermine in complete virus particles but not in their respective top components. The polyamines, with spermidine predominant, comprise 1.41% of the virus particle by weight, which is sufficient to neutralize 26% of the single-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.21.1.408-410.1977
更新日期:1977-01-01 00:00:00
abstract::In vitro studies have indicated that retroviral nucleocapsid (NC) protein facilitates both DNA synthesis by reverse transcriptase (RT) and annealing of the nascent DNA with acceptor template. Increasing the rate of DNA synthesis is expected to reduce the frequency of RT template switching, whereas annealing the nascen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.15.7473-7484.2002
更新日期:2002-08-01 00:00:00
abstract::Phosphorylation of the murine mammary tumor virus (MuMTV) structural proteins was studied in an MuMTV-infected epithelial cell line derived from a BALB/cf C3H mouse mammary tumor. Immunoprecipitation of 32P-labeled cell extracts with monospecific anti-p27 serum revealed that phosphorylation occurred at the stage of th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.30.1.241-247.1979
更新日期:1979-04-01 00:00:00
abstract::The limited efficiency of in vivo gene transfer by replication-deficient retroviral vectors remains an obstacle to achieving effective gene therapy for solid tumors. One approach to circumvent this problem is the use of replication-competent retroviral vectors. However, the application of such vectors is at a comparat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02470-06
更新日期:2007-07-01 00:00:00
abstract::In vitro transcription by vesicular stomatitis virus nucleocapsids is inhibited by enzymatic dephosphorylation of the NS protein. We provide evidence that specific, partial dephosphorylation of NS molecules is the only detectable change in nucleocapsids treated with bacterial alkaline phosphatase under conditions that...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.43.1.104-112.1982
更新日期:1982-07-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) Tat is a mediator of viral transcription and is involved in the control of virus replication. However, associations between HIV-1 Tat diversity and functional effects during primary HIV-1 infection are still unclear. We estimated selection pressures in tat exon 1 using the m...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03297-12
更新日期:2013-05-01 00:00:00
abstract::The tsB5 mutant of herpes simplex virus type 1 (HSV-1) strain HFEM was shown previously to be temperature sensitive for accumulation of the mature form of glycoprotein gB, for production or activity of a factor required in virus-induced cell fusion, and for production of virions with normal levels of infectivity. In a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.35.1.114-128.1980
更新日期:1980-07-01 00:00:00
abstract::Processing of dengue virus type 2 polyprotein precursor NS3-NS4A-NS4B-NS5 could be mediated by the catalytically active NS3 protease domain and NS2B in trans at the dibasic sites NS3-NS4A and NS4B-NS5. Subcellular localization of the unprocessed precursor NS3-NS4A-NS4B-NS5 showed that it was confined to a distinct sub...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.12.7549-7554.1992
更新日期:1992-12-01 00:00:00
abstract::In a previous study (S. Zheng, G. N. Woode, D. R. Melendy, and R. F. Ramig, J. Clin. Microbiol. 27:1939-1945, 1989), it was predicted that the VP7 serotype 6 bovine rotavirus strains NCDV and B641 do not share antigenically similar VP4s. In this study, gene 4 and the VP7 gene of B641 were sequenced, and the amino acid...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.10.5535-5538.1991
更新日期:1991-10-01 00:00:00
abstract::We have previously described the expression of the major nonstructural protein (NS-1) of Aleutian mink disease parvovirus (ADV) in insect cells by using a baculovirus vector (J. Christensen, T. Storgaard, B. Bloch, S. Alexandersen, and B. Aasted, J. Virol. 67:229-238, 1993). To study its biochemical properties, ADV NS...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.3.1802-1809.1995
更新日期:1995-03-01 00:00:00
abstract::Defined segments of the cloned foot-and-mouth disease virus genome corresponding to all parts of the coding region were expressed in Escherichia coli as fusions to the N-terminal part of the MS2-polymerase gene under the control of the inducible lambda PL promoter. All constructs yielded large amounts of proteins, whi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.3.983-991.1986
更新日期:1986-03-01 00:00:00
abstract::Temperature-sensitive (ts) mutants of vesicular stomatitis virus belonging to complementation groups I, II and IV inhibited the replication of wild-type vesicular stomatitis virus when mixed infections were carried out in BHK21 cells at 32, 37, and 39.5 C. The group IV mutant (ts G 41) was most effective in this regar...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.19.1.102-107.1976
更新日期:1976-07-01 00:00:00
abstract::The S2 gene of bluetongue virus, serotype 17, has been cloned, and the nonstructural protein NS2 has been expressed. Synthetic peptides matching regions within the amino acid sequence of NS2 were used to map three single-stranded RNA (ssRNA)-binding regions within the protein. A prokaryotic expression system was then ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.2.499-506.2002
更新日期:2002-01-01 00:00:00
abstract::The Tax protein from human T-cell leukemia virus type I (HTLV-I) is a 40-kDa phosphoprotein capable of activating transcription from its own long terminal repeat (LTR), as well as increasing the transcription of cellular genes. Transcriptional activation of the HTLV-I LTR has been demonstrated via a cyclic-AMP-respons...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.7.4436-4441.1993
更新日期:1993-07-01 00:00:00
abstract::We previously described that type B retrovirus-like particles released from the human mammary carcinoma cell line T47D are pseudotypes and package retroviral RNA of different origins (W. Seifarth, H. Skladny, F. Krieg-Schneider, A. Reichert, R. Hehlmann, and C. Leib-Mösch, J. Virol. 69:6408-6416, 1995). One preferenti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.10.8384-8391.1998
更新日期:1998-10-01 00:00:00