Abstract：
:We previously reported prolonged HIV-1 transcriptional gene silencing by an RNA duplex targeting a sequence located within the NF-kappaB binding motif of the HIV-1 promoter in a susceptible HeLa cell line. Here we report extremely prolonged suppression of productive HIV-1 infection in a T-cell line (Molt-4) by a retrovirally delivered short-hairpin RNA (shRNA) targeting the same region (shkappaB). Following retroviral delivery of an shRNA we established shRNA-expressing CD4(+) T-cell lines. HIV-1 gene expression was profoundly suppressed for 1 year. Results of nuclear run-on assays and HIV-1 LTR-luciferase reporter assays revealed that shkappaB acted by inhibition of HIV-1 transcription. The effect was reversed by a histone deacetylase inhibitor, trichostatin-A (TSA), but not by a DNA methyltransferase inhibitor, 5-azacytidine (5-AzaC). Furthermore, chromatin immunoprecipitation assays (ChIP) demonstrated rapid, sustained induction of heterochromatin structures within the HIV-1 promoter region, with enrichment of histone 3 lysine 27 tri-methylation (H3K27me3) and H3K9 methylation. H3K27me3 enrichment was the most pronounced. This prolonged suppression could not be recapitulated by either retrovirally delivered anti-sense or sense strands alone or in combination. Our data strongly suggest that shkappaB induces high level, sustained transcriptional gene silencing of HIV-1 and offers the possibility of new therapeutic strategies.
journal_name
Microbes Infectjournal_title
Microbes and infectionauthors
Yamagishi M,Ishida T,Miyake A,Cooper DA,Kelleher AD,Suzuki K,Watanabe Tdoi
10.1016/j.micinf.2009.02.003subject
Has Abstractpub_date
2009-04-01 00:00:00pages
500-8issue
4eissn
1286-4579issn
1769-714Xpii
S1286-4579(09)00018-5journal_volume
11pub_type
杂志文章abstract：:Cytokines are increasingly recognized as important components of the cellular immune responses to intracellular pathogens. In this study, we analyzed the production of TGF-beta, IL-10 and IFN-gamma by PBMC of unexposed naïve subjects and LCL patients after stimulation with live Leishmania guyanensis (L.g.). We demonst...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2007.04.009
更新日期：2007-07-01 00:00:00
abstract：:Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs) and in the induction of immune responses. However, relatively little is known about their functions in innate/acquired responses to complex eukaryotic microorganisms, including helminth parasites. That Sch...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2007.09.013
更新日期：2007-11-01 00:00:00
abstract：:Streptococcus pneumoniae is a major pathogen causing potentially life-threatening community-acquired diseases in both the developed and developing world. Since 1967, there has been a dramatic increase in the incidence of penicillin-resistant and multiply antibiotic-resistant pneumococci worldwide. Prevention of access...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/s1286-4579(00)01345-9
更新日期：2000-12-01 00:00:00
abstract：:Leprosy is a chronic infection of the skin and nerves caused by Mycobacterium leprae. Erythema nodosum leprosum (ENL) is a reactive state in lepromatous leprosy. Thalidomide has been used to treat ENL since the 1960s. One of its mechanisms of action is anti-inflammatory through selective inhibition of the pro-inflamma...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/s1286-4579(02)01645-3
更新日期：2002-09-01 00:00:00
abstract：:The Gram-negative bacterium Burkholderia cepacia has recently emerged as an important opportunistic pathogen in humans. This review focuses on the cellular aspects of B. cepacia infection and the dynamics of the B. cepacia-host cell interaction, including recent advances in our understanding of the ability of B. cepac...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/s1286-4579(01)01389-2
更新日期：2001-04-01 00:00:00
abstract：:Viral protein R (Vpr), an accessory protein of human immunodeficiency virus type 1 (HIV-1), induces the G2 cell cycle arrest in fission yeast for which host factors, such as Wee1 and Rad24, are required. Catalyzing the inhibitory phosphorylation of Cdc2, Wee1 is known to serve as a major regulator of G2/M transition i...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2006.08.003
更新日期：2006-10-01 00:00:00
abstract：:Yersiniabactin (Ybt) is a siderophore-dependent iron uptake system encoded on a pathogenicity island that is widespread among pathogenic bacteria including the Yersiniae. While biosynthesis of the siderophore has been elucidated, the secretion mechanism and a few components of the uptake/utilization pathway are uniden...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/j.micinf.2011.04.008
更新日期：2011-09-01 00:00:00
abstract：:The intestine is inhabited by a diverse range of microorganisms, which requires the host to employ numerous barrier measures to prevent bacterial invasion. However, the intestinal microbiota additionally acts symbiotically with host cells to maintain epithelial barrier function, and perturbation to this interaction pl...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2020.10.009
更新日期：2020-11-12 00:00:00
abstract：:Pathogenic Leptospira species are the causative agents of leptospirosis, a global zoonotic infectious disease. Toxin-antitoxin (TA) modules have been confirmed as stress-response elements that induce prokaryotic and eukaryotic cell-growth arrest or death, but their role in the virulence of Leptospira has not been repo...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2014.10.010
更新日期：2015-01-01 00:00:00
abstract：:A common theme in bacterial disease is the manipulation of the eukaryotic cytoskeleton by pathogenic factors. Understanding how virulence factors operate to achieve these alterations is a growing and important research effort. This review focuses on several virulence factors from the pathogen Salmonella, and considers...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/j.micinf.2004.08.001
更新日期：2004-11-01 00:00:00
abstract：:Denaturing high-performance liquid chromatography (DHPLC) is a relatively new technique, which utilizes heteroduplex formation between wild-type and mutated DNA strands to identify point mutations. Heteroduplex molecules are separated from homoduplex molecules by ion-pair, reverse-phase liquid chromatography on a spec...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2005.06.008
更新日期：2006-01-01 00:00:00
abstract：:Superinfection rates of human immunodeficiency virus type 1 (HIV-1) have increasingly been leading to more variation in HIV-1, as evidenced by the emergence of circulating recombinant forms (CRFs). We recently reported complementation in a persistently replication-defective subtype B-infected cell clone, L-2, by super...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2008.01.012
更新日期：2008-04-01 00:00:00
abstract：:Zika virus (ZIKV) greatly impacted the international scientific and public health communities in the last two years due to its association with microcephaly and other neonatal alterations. This review will discuss lessons learned from viral pathogenesis, epidemiology and clinical findings observed during the ZIKV outb...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/j.micinf.2018.02.008
更新日期：2018-12-01 00:00:00
abstract：:Campylobacter jejuni is the predominant cause of antecedent infection in Guillain-Barré syndrome (GBS) or Miller Fisher syndrome (MFS). C. jejuni probably triggers GBS or MFS through molecular mimicry between bacterial sialylated lipo-oligosaccharides (LOS) and gangliosides in peripheral nerve tissue. We investigated ...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2005.06.022
更新日期：2006-01-01 00:00:00
abstract：:Erythritol is a four-carbon sugar preferentially utilized by Brucella spp. The presence of erythritol in the placentas of goats, cows, and pigs has been used to explain the localization of Brucella to these sites and the subsequent accumulation of large amounts of bacteria, eventually leading to abortion. Here we show...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2013.02.002
更新日期：2013-06-01 00:00:00
abstract：:The PE and PPE family of proteins of Mycobacterium tuberculosis have been hypothesized to play important roles in the biology of the organism and some proteins have been shown to be involved in eliciting T-cell responses. Earlier, we had identified putative HLA class I binding epitopes of the PE and PPE proteins of My...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2008.04.017
更新日期：2008-07-01 00:00:00
abstract：:Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis (Pb), a thermal dimorphic fungus. Its major antigen is a 43-kDa glycoprotein. Gp43 embodies different functions: it participates in evasion mechanisms during the installation of primary infection, stimulates granul...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2008.10.011
更新日期：2009-01-01 00:00:00
abstract：:The 3'-5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue i...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/j.micinf.2012.04.011
更新日期：2012-08-01 00:00:00
abstract：:Very recently, a new avian flu outbreak in humans, which is caused by a novel H7N9 influenza A virus (AIV), was reported in China. As of April 13, 2013, 49 confirmed cases (mainly middle-aged to elderly males), including 11 deaths, were reported in China. Here we analyzed the genomic signatures and protein sequences o...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2013.04.004
更新日期：2013-06-01 00:00:00
abstract：:Tonsilloliths are a potential cause of oral malodor. In this study, microbial profiles and composition of tonsilloliths were determined using culture-independent molecular methods and scanning electron microscopy. 16S ribosomal RNA bacterial genes (16S rDNAs) isolated from tonsilloliths of 6 individuals were amplified...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2006.04.023
更新日期：2006-08-01 00:00:00
abstract：:Although the pathogenesis of periodontal disease (PD) is not well known, cytokines, chemotactic factors and inflammatory cells are certainly involved in the disease outcome. Here, we characterized the evolution of the PD induced by Actinobacillus actinomycetemcomitans in mice, showing that oral inoculation of these ba...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2005.01.012
更新日期：2005-04-01 00:00:00
abstract：:Episomal expression of the major surface glycoprotein (gp63) sense and antisense mRNAs in Leishmania amazonensis was found previously to modulate the expression of this molecule as well as its infection of macrophages in vitro. Here, we evaluated the in vivo infectivity of these transfectants in BALB/c mice. Antisense...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2006.01.006
更新日期：2006-05-01 00:00:00
abstract：:The bacteria-phagocyte interaction is of central importance in Salmonella pathogenesis. Immediately following phagocytosis, the NADPH phagocyte oxidase complex assembles in vesicles and produces highly toxic reactive oxygen species that play a major role in initial Salmonella killing by phagocytes. However, Salmonella...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/s1286-4579(01)01492-7
更新日期：2001-11-01 00:00:00
abstract：:Lactobacilli are normal inhabitants of our microbiota and are known to protect against pathogens. Neisseria gonorrhoeae is a human specific pathogenic bacterium that colonises the urogenital tract where it causes gonorrhoea. In this study we analysed early interactions between lactobacilli and gonococci and investigat...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2008.07.032
更新日期：2008-10-01 00:00:00
abstract：:This review summarizes and discusses virulence mechanisms whereby Porphyromonas gingivalis can persist in the oral cavity. It is proposed that the virulence of P. gingivalis is dependent, at least in part, upon its ability to establish a complex host-pathogen molecular crosstalk which subverts innate immunity. The sop...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/j.micinf.2009.03.009
更新日期：2009-05-01 00:00:00
abstract：:Nonsense-mediated mRNA decay (NMD) is an essential and conserved cellular mRNA quality control mechanism. RNA signals to express viral genes from overlapping open reading frames potentially initiate NMD, nevertheless it is not clear whether viral RNAs are sensitive to NMD or if viruses have evolved mechanisms to evade...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2013.03.006
更新日期：2013-06-01 00:00:00
abstract：:Enterovirus 71 (EV71) is a neurotropic pathogen that can cause severe neural diseases and complications on infected patients. Clinical observations showed that EV71-induced immune responses may be associated with virus induced neurogenic pulmonary edema. Here reviewed studies that discovered several host molecules as ...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/j.micinf.2010.03.006
更新日期：2010-07-01 00:00:00
abstract：:CD4(+)CD25(+) T cells regulate the activity of autoreactive T cells. Depletion of these cells results in the development of a wide-spectrum of organ-specific autoimmune diseases. In vitro model systems have been developed to study the function of these potent suppressor cells. Following their activation via their T-ce...
journal_title：Microbes and infection
pub_type： 杂志文章,评审
doi：10.1016/s1286-4579(01)01453-8
更新日期：2001-09-01 00:00:00
abstract：:Recombinant BCG strain that secretes the chimaeric protein of Ag85B and ESAT-6 has been demonstrated to augment Th1 immune response in C57BL/6 mice. In this paper, we studied the immunostimulatory activity of the recombinant BCG strains in vitro and found out that rBCG-A(N)-E-A(C) activated THP-1 cells and induced hig...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2010.04.002
更新日期：2010-08-01 00:00:00
abstract：:Using a viral-induced immunopathology model, we showed that when CD4(+) T cells were allowed to undergo homeostatic expansion prior to ocular herpes simplex virus infection, mice developed more severe inflammatory lesions with the increased severity associated with enhanced effector function of ocular CD4(+) T cells, ...
journal_title：Microbes and infection
pub_type： 杂志文章
doi：10.1016/j.micinf.2008.06.012
更新日期：2008-08-01 00:00:00
