Abstract:
:The Rev protein of HIV-1, which facilitates the nuclear export of HIV-1 pre-mRNAs, has been a target for antiviral therapy. Here we describe a new strategy for inhibiting Rev function and HIV-1 replication. In contrast to previous approaches, we use a wild-type rather than a mutant Rev protein and covalently link this Rev sequence to the NS1 protein of influenza A virus, a protein that inhibits the nuclear export of mRNAs. The NS1 protein contains an RNA-binding domain mutation (RM), so that the only functional RNA-binding domain in the chimeric protein (NS1RM-Rev) is in the Rev protein sequence. In the presence of the NS1RM-Rev chimeric protein, HIV-1 pre-mRNAs were retained in, rather than exported from, the nucleus. In addition, this chimeric protein effectively inhibited Rev function in trans in transfection experiments and effectively inhibited the production of HIV-1 in tissue culture cells transfected with an infectious molecular clone of HIV-1 DNA. The inhibitory activities of the NS1RM-Rev chimera were at least equivalent to those of the Rev M10 mutant protein, which has been considered to be the prototype trans inhibitor of Rev function and is currently in phase I clinical trials for the treatment of AIDS patients. We discuss (i) the potential for increasing the inhibitory activity of NS1-Rev chimeras against HIV-1 and (ii) the need for additional studies to evaluate these chimeras for the treatment of AIDS.
journal_name
Proc Natl Acad Sci U S Aauthors
Qian XY,Chen ZY,Zhang J,Rabson AB,Krug RMdoi
10.1073/pnas.93.17.8873subject
Has Abstractpub_date
1996-08-20 00:00:00pages
8873-7issue
17eissn
0027-8424issn
1091-6490journal_volume
93pub_type
杂志文章abstract::Nasopharyngeal carcinoma (NPC) most frequently occurs in southern China and southeast Asia. Epidemiology studies link NPC to genetic predisposition, Epstein-Barr virus (EBV) infection, and environmental factors. Genetic studies indicate that mutations in chromatin-modifying enzymes are the most frequent genetic altera...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1705236114
更新日期:2017-09-05 00:00:00
abstract::One of the most fundamental functions of the brain is to predict upcoming events on the basis of the recent past. A closely related function is to signal when a prediction has been violated. The identity of the brain regions that mediate these functions is not known. We set out to determine whether they are implemente...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1112895108
更新日期:2011-11-29 00:00:00
abstract::The embryonic sites in which progenitors of the hematopoietic lineages first emerge are ideal regions to characterize both the cells and environment needed to initiate blood cell development. For a number of years both the murine yolk sac and embryo have been recognized to contain progenitors of B lymphocytes. However...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.14.6429
更新日期:1993-07-15 00:00:00
abstract::The high concentration of gonadotropin-releasing hormone (GnRH) in milk of several species implies that the mammary gland is either a site of synthesis for this neuropeptide or that it is efficiently concentrated from plasma by this organ. By PCR amplification of mammary gland cDNA, we have demonstrated expression of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.11.4994
更新日期:1994-05-24 00:00:00
abstract::Gastrointestinal infections often induce epithelial damage that must be repaired for optimal gut function. While intestinal stem cells are critical for this regeneration process [R. C. van der Wath, B. S. Gardiner, A. W. Burgess, D. W. Smith, PLoS One 8, e73204 (2013); S. Kozar et al., Cell Stem Cell 13, 626-633 (2013...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1915255117
更新日期:2020-04-07 00:00:00
abstract::The ability of estrogens to stimulate the transcriptional activity of the estrogen receptor can be inhibited by a diverse range of estrogen antagonists. Here we show that the antiestrogen ICI 164,384, N-(n-butyl)-11-[3,17 beta-dihydroxy-estra-1,3,5(10)-trien-7 alpha-yl]N-methylundecanamide, rapidly reduces the levels ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.9.4037
更新日期:1992-05-01 00:00:00
abstract::The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed "nutritional immunity." CP binds Mn(2+) and Zn(2+) with high affinity and starves bacteria of these essential nutrients. Combining biophysical, structural, and microbiological analysis, we identified ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1220341110
更新日期:2013-03-05 00:00:00
abstract::Loss-of-function DJ-1 mutations can cause early-onset Parkinson's disease. The function of DJ-1 is unknown, but an acidic isoform accumulates after oxidative stress, leading to the suggestion that DJ-1 is protective under these conditions. We addressed whether this represents a posttranslational modification at cystei...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402959101
更新日期:2004-06-15 00:00:00
abstract::Activation of eukaryotic class II gene expression involves the formation of a transcription initiation complex that includes RNA polymerase II, general transcription factors, and SRB components of the holoenzyme. Negative regulators of transcription have been described, but it is not clear whether any are general repr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.7.3145
更新日期:1997-04-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) have been found as monomers but also as dimers or higher-order oligomers in cells. The relevance of the monomeric or dimeric receptor state for G protein activation is currently under debate for class A rhodopsin-like GPCRs. Clarification of this issue requires the availability of w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0705312104
更新日期:2007-07-17 00:00:00
abstract::The RNA synthesized in vitro by the virion-associated RNA-instructed RNA polymerase of purified vesicular stomatitis virus contains polyadenylate sequences. These have been demonstrated by their partial resistance to pancreatic and T(1) ribonucleases and their capacity to bind to poly(U) filters and oligo(dT)-cellulos...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.12.3566
更新日期:1973-12-01 00:00:00
abstract::The rationale for genome-wide association study (GWAS) results is sequence variation in cis-regulatory elements (CREs) modulating a target gene's expression as the major cause of trait variation. To understand the complete molecular landscape of one of these GWAS loci, we performed in vitro reporter screens in cardiom...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1808734116
更新日期:2019-05-28 00:00:00
abstract::Higher acenes have drawn much attention as promising organic semiconductors with versatile electronic properties. However, the nature of their ground state and electronic excited states is still not fully clear. Their unusual chemical reactivity and instability are the main obstacles for experimental studies, and the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1606021113
更新日期:2016-08-30 00:00:00
abstract::During latent infection of humans with Mycobacterium tuberculosis, bacteria persist in the asymptomatic host within granulomas, organized collections of differentiated macrophages, and other immune cells. The mechanisms for persistence remain poorly understood, as is the metabolic and replicative state of the microbes...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.002024599
更新日期:2002-03-19 00:00:00
abstract::Guinea pigs were immunized with liposomal model membranes containing phosphatidylethanolamine (PE) or glycerophosphorylethanolamine (GPE) derivatives in which the amino function was substituted with either dinitrophenylaminocaproyl (Dnp-Cap) or mono(p-azobenzenearsonic acid)tyrosyl (ABA-Tyr) residues. Previous studies...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.11.4582
更新日期:1975-11-01 00:00:00
abstract::Auditory speech perception enables listeners to access phonological categories from speech sounds. During speech production and speech motor learning, speakers' experience matched auditory and somatosensory input. Accordingly, access to phonetic units might also be provided by somatosensory information. The present st...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1911142117
更新日期:2020-03-17 00:00:00
abstract::Most, but not all, aged rats exhibit a profound deficit in spatial memory when tested in a radial maze--a task known to depend on the integrity of the hippocampal formation. In this study, animals were divided into three groups based on their spatial memory capacity: young adult rats with good memory, aged rats with i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.9.3027
更新日期:1986-05-01 00:00:00
abstract::Experimental circular dichroic (CD) spectra of three proteins have been combined with estimates of the content of peptide-chain structural modes obtained from x-ray diffraction studies of the same proteins. Solution of the simultaneous equations at a series of wavelengths permits the construction of a CD spectrum for ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.5.969
更新日期:1971-05-01 00:00:00
abstract::Inactivation of the retinoblastoma gene (RB gene) is associated with the development of several human malignancies including retinoblastomas, some osteo- and soft tissue sarcomas, small cell lung cancer, and possibly breast and bladder cancers. To our knowledge, this gene has not been evaluated in human germ-cell mali...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.15.6662
更新日期:1991-08-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1911761117
更新日期:2020-03-24 00:00:00
abstract::Plasmonics now delivers sensors capable of detecting single molecules. The emission enhancements and nanometer-scale optical confinement achieved by these metallic nanostructures vastly increase spectroscopic sensitivity, enabling real-time tracking. However, the interaction of light with such nanostructures typically...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1914713117
更新日期:2020-02-04 00:00:00
abstract::It is unknown whether cross-regulatory interactions between homeotic genes, which have been shown to play an important role in the maintenance of their expression domains during Drosophila development, are also important during mammalian development. We have analyzed here the expression of Hox genes in Hoxa-1 (Hox-1.6...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.16.7666
更新日期:1993-08-15 00:00:00
abstract::We describe two collaborations in which psychologists and economists provided essential support on foundational projects in major research programs. One project involved eliciting adolescents' expectations regarding significant future life events affecting their psychological and economic development. The second proje...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1615461114
更新日期:2017-03-28 00:00:00
abstract::Delayed gastric ulcer healing is a well recognized problem associated with the use of cyclooxygenase (COX) inhibitors. In contrast, NO-releasing COX inhibitors do not interfere with ulcer healing. These divergent effects may in part be due to differences in their effects on platelets, which are known to influence ulce...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.202392199
更新日期:2002-10-01 00:00:00
abstract::In the plant Nicotiana plumbaginifolia, manganese superoxide dismutase (MnSOD) is synthesized in the cytoplasm as a preprotein and is subsequently translocated to the mitochondrial matrix with corresponding cleavage of an NH2-terminal leader sequence. To determine whether the plant enzyme could replace the endogenous ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.9.3237
更新日期:1989-05-01 00:00:00
abstract::We investigated the manner in which the sea urchin larva takes up calcium from its body cavity into the primary mesenchymal cells (PMCs) that are responsible for spicule formation. We used the membrane-impermeable fluorescent dye calcein and alexa-dextran, with or without a calcium channel inhibitor, and imaged the la...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1612017113
更新日期:2016-11-08 00:00:00
abstract::Inferring causal effects from observational and interventional data is a highly desirable but ambitious goal. Many of the computational and statistical methods are plagued by fundamental identifiability issues, instability, and unreliable performance, especially for large-scale systems with many measured variables. We...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1510493113
更新日期:2016-07-05 00:00:00
abstract::Double-stranded RNA (dsRNA) recently has been shown to give rise to genetic interference in Caenorhabditis elegans and also is likely to be the basis for phenotypic cosuppression in plants in certain instances. While constructing a plasmid vector for transfection of trypanosome cells, we serendipitously discovered tha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.25.14687
更新日期:1998-12-08 00:00:00
abstract::The rigidity of numerous biological filaments and crafted microrods has been conveniently deduced from the analysis of their thermal fluctuations. However, the difficulty of measuring nanometric displacements with an optical microscope has so far limited such studies to sufficiently flexible rods, of which the persist...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1608697114
更新日期:2017-03-07 00:00:00
abstract::We provide evidence for an interaction between mouse class I major histocompatibility complex antigens and insulin receptors. Antibodies against class I but not class II major histocompatibility complex antigens immunoprecipitate photoaffinity-labeled hepatic insulin receptors. Haplotype specificity is demonstrated by...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.10.3474
更新日期:1986-05-01 00:00:00