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Xiao-Hong Wang

Publications and source records attributed to Xiao-Hong Wang.

At least 19 recordsLinked to original sources
PubMed2006

RNA interference directs innate immunity against viruses in adult Drosophila.

Innate immunity against bacterial and fungal pathogens is mediated by Toll and immune deficiency (Imd) pathways, but little is known about the antiviral response in Drosophila. Here, we demonstrate that an RNA interference pathway protects adult flies from infection by two evolutionarily diverse viruses. Our work also describes a molecular framework for the viral immunity, in which viral double-stranded RNA produced during infection acts as the pathogen trigger whereas Drosophila Dicer-2 and Argonaute-2 act as host sensor and effector, respectively. These findings establish a Drosophila model for studying the innate immunity against viruses in animals.

Animals↗
PubMed2006

Cross-clade neutralizing activity of human anti-V3 monoclonal antibodies derived from the cells of individuals infected with non-B clades of human immunodeficiency virus type 1.

The majority of global human immunodeficiency virus infections are caused by viruses characterized by a GPGQ motif at the tip of the V3 loop. Characterization of anti-V3 monoclonal antibodies (MAbs) that neutralize isolates with the GPGQ V3 motif is an important step in designing vaccines that will induce such Abs. Consequently, seven human anti-V3 MAbs derived from the cells of individuals infected with non-B-subtype viruses (anti-V3(non-B) MAbs) were generated from the cells of individuals from Africa infected with circulating recombinant forms CRF02_AG, CRF09_cpx, and CRF13_cpx, each of which contains a subtype A env gene. Sequence analysis of plasma viruses revealed a GPGQ motif at the apex of the V3 loop from six of the seven subjects and a GPGR motif from one subject. The MAbs were selected with fusion proteins (FP) containing V3(92UG037.8) or V3(JR-CSF) from subtype A or B, respectively. In virus binding assays, five of the seven (71%) anti-V3(non-B) MAbs bound to V3-FPs from both subtype A and subtype B, while only four of the nine (44%) anti-V3(B) MAbs recognized both V3-FPs. Using two neutralization assays, both the anti-V3(non-B) and the anti-V3(B) MAbs neutralized subtype B viruses with similar activities, while the anti-V3(non-B) MAbs exhibited a tendency toward both increased potency and breadth of neutralization against non-B viruses compared to anti-V3(B) MAbs. Statistical significance was not achieved, due in large measure to the sizes of the MAb panels, but the overall pattern of data strongly suggests that viruses with the GPGQ motif at the tip of the V3 loop induce anti-V3 Abs with broader cross-neutralizing activity than do viruses with the GPGR motif.

Amino Acid Motifs↗
PubMed2006

[Study on apoptosis of oral squamous carcinoma cell line KB and KBv200 induced by survivin RNAi].

BACKGROUND & OBJECTIVE: Survivin, a member of IAPs (inhibition of apoptosis proteins) family, has been revealed by many studies to inhibit the activation of caspase-3, caspase-7 and caspase-9, and thus increase the anti-apoptotic effect of cancer cells, which subsequently makes the cells to become resistant to chemotherapy in cancer treatment. Survivin is expressed in human oral squamous carcinoma cell line KB and its multiple-drug resistant (MDR) cell line KBv200. This study was to compare the apoptosis induced by silencing survivin gene between these two squamous cell lines. METHODS: Mu6/survivin plasmid which expressed shRNA against survivin was transfected into both KB and KBv200 cells to inhibit the expression of survivin gene. Survivin mRNA and protein expression was detected by semi-quantitative RT-PCR and flow cytometry (FCM), respectively. Cell apoptotic rate was measured by flow cytometry after PI staining, and apoptotic morphology of cells was observed under a fluorescent microscope after Hoechst33258 staining. Activation of caspase-3 was measured by colorimetric assay. MTT was used to evaluate the growth inhibition of tumor cells. RESULTS: Expression of survivin, which was higher in KBv200 at mRNA and protein level, was detected in both KB and KBv200. After 48 h transfection with mu6/survivin plasmid, the expression level of survivin mRNA in KB and KBv200 was reduced by (61.98+/-8.12)% and (59.29+/-6.32)%; and that of survivin protein was decreased by (44.25+/-5.26)% and (38.76+/-4.31)% compared with the control group. Moreover, KB and KBv200 cells exhibited typical apoptotic cell morphology by Hoechst 33258 staining. Apoptosis, which was higher in KB cells, was increased significantly at 24, 48, 72 h after the transfection of mu6/surviving in KB and KBv200 cells, and reached the peak at 48 h. Similarly, activation of caspase-3 was elevated significantly, and reached the peak at 48 h. MTT assay revealed the inhibitory rates were (33.04+/-2.16)%, (56.25+/-3.32)% and (58.26+/-5.14)% in KB cells, and (35.23+/-3.42)%, (44.90+/-4.12)% and (44.19+/-4.37)% in KBv200 cells at 24, 48, 72 h after the transfection, respectively. Growth rate was lower in KB cells at 48, 72 h after the transfection compared with KBv200 cells. CONCLUSION: RNA interference could silence the expression of survivin, which significantly induces apoptosis not only in KB cells, but also in drug resistant KBv200 cells.

Antineoplastic Agents↗
PubMed2005

Cellular immune selection with hepatitis C virus persistence in humans.

Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific cellular immune responses. To determine if immunologically driven sequence variation occurs with HCV persistence, we coordinately analyzed sequence evolution and CD8+ T cell responses to epitopes covering the entire HCV polyprotein in subjects who were followed prospectively from before infection to beyond the first year. There were no substitutions in T cell epitopes for a year after infection in a subject who cleared viremia. In contrast, in subjects with persistent viremia and detectable T cell responses, we observed substitutions in 69% of T cell epitopes, and every subject had a substitution in at least one epitope. In addition, amino acid substitutions occurred 13-fold more often within than outside T cell epitopes (P < 0.001, range 5-38). T lymphocyte recognition of 8 of 10 mutant peptides was markedly reduced compared with the initial sequence, indicating viral escape. Of 16 nonenvelope substitutions that occurred outside of known T cell epitopes, 8 represented conversion to consensus (P = 0.015). These findings reveal two distinct mechanisms of sequence evolution involved in HCV persistence: viral escape from CD8+ T cell responses and optimization of replicative capacity.

Amino Acid Substitution↗
PubMed2005

Divergent and convergent evolution after a common-source outbreak of hepatitis C virus.

The genomic sequences of viruses that are highly mutable and cause chronic infection tend to diverge over time. We report that these changes represent both immune-driven selection and, in the absence of immune pressure, reversion toward an ancestral consensus. Sequence changes in hepatitis C virus (HCV) structural and nonstructural genes were studied in a cohort of women accidentally infected with HCV in a rare common-source outbreak. We compared sequences present in serum obtained 18-22 yr after infection to sequences present in the shared inoculum and found that HCV evolved along a distinct path in each woman. Amino acid substitutions in known epitopes were directed away from consensus in persons having the HLA allele associated with that epitope (immune selection), and toward consensus in those lacking the allele (reversion). These data suggest that vaccines for genetically diverse viruses may be more effective if they represent consensus sequence, rather than a human isolate.

Alleles↗
PubMed2005

Sustained low-level expression of interferon-gamma promotes tumor development: potential insights in tumor prevention and tumor immunotherapy.

Although the proinflammatory cytokine interferon-gamma (IFN-gamma) has been generally thought to enhance antitumor immune responses and be involved in antitumor mechanisms of many other immunotherapy molecules, it has also been reported that IFN-gamma could promote tumor immune evasion. In this report, by using an ideal mouse model that expresses IFN-gamma locally in muscle, we demonstrate that sustained low-level expression of IFN-gamma promotes the development of several types of tumor including H22 hepatoma, MA782/5S mammary adenocarcinoma and B16 melanoma. However, transitory expression of IFN-gamma does not have such an effect. On the other hand, sustained high-level expression of IFN-gamma mediates significant antitumor effect on H22 hepatoma. Low level of IFN-gamma upregulates expression of PD-L1, PD-L2, CTLA-4 and Foxp3, which may partly account for the tumor immune evasion promoted by IFN-gamma. Furthermore, blockade of PD-L inhibits IFN-gamma's tumor-promoting effect. Our findings provide a mechanistic link between chronic inflammation and cancer and would have potential implications for cancer prevention and also for the design of cytokine-based cancer immunotherapy.

Adenocarcinoma↗
PubMed2005

Identification of a new quaternary neutralizing epitope on human immunodeficiency virus type 1 virus particles.

The selection of human monoclonal antibodies (MAbs) specific for human immunodeficiency virus (HIV) type 1 by binding assays may fail to identify Abs to quaternary epitopes on the intact virions. The HIV neutralization assay was used for the selection of human MAb 2909, which potently neutralizes SF162 and recognizes an epitope on the virus surface but not on soluble proteins. Three regions of gp120, the V2 and V3 loops and the CD4 binding domain, contribute to the epitope recognized by MAb 2909. The existence of such a unique MAb, which defines a complex epitope formed by a quaternary structure, suggests that there may be other new neutralizing HIV epitopes to target with vaccines.

Antibodies, Monoclonal↗
PubMed2005

Tight association of hepatocellular carcinoma with HBV infection in North China.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cancer in China. Hepatitis B and C viruses (HBV and HCV) and aflatoxins are known risk factors for HCC, but the etiological status of these factors in HCC development is not clear. This study was undertaken to define the absolute importance of HBV in hepatocarcinogenesis of North China. METHODS: A consecutive series of 119 patients with pathologically proven HCC were collected from North China during January 1998 to December 2000 by the Cancer Hospital of the Chinese Academy of Medical Sciences, Beijing. Serum HBsAg, anti-HBc and anti-HCV were negative HBV sero-markers. The HBV X gene was analyzed for its expression by PCR, DNA sequencing, and immunohistochemistry. RESULTS: In the 119 HCC patients, 82.4% (98/119) were HBsAg seropositive. When a comprehensive set of HBV markers were detected, the HBV infection rate in these HCC patients was 99.2% (118/119). Of the patients, 11.8%(14/119) were found to be anti-HCV positive. But all the anti-HCV positive HCC patients were co-infected with HBV. CONCLUSIONS: HBV infection is virtually ubiquitous in HCC patients in North China. The tight association of HBV with HCC strongly suggests the dominant role of HBV infection in causing hepatocellular carcinoma. About 11.8% of HCC patients being HCV-related are co-infected with HBV.

Adult↗
PubMed2004

Blocking programmed death-1 ligand-PD-1 interactions by local gene therapy results in enhancement of antitumor effect of secondary lymphoid tissue chemokine.

The negative signal provided by interactions of programmed death-1 (PD-1) and its ligands, costimulatory molecules PD-L1 (also B7-H1) and PD-L2 (also B7-DC), is involved in the mechanisms of tumor immune evasion. In this study, we found that this negative signal was also involved in immune evasion in tumor immunotherapy. When we used different doses of a constructed eukaryotic expression plasmid, pSLC, which expresses functional murine secondary lymphoid tissue chemokine (SLC, CCL21), to treat BALB/c mice inoculated with H22 murine hepatoma cells, the inhibitory effect was enhanced along with the increase of pSLC dosage. Unexpectedly, however, the best complete inhibition rate of tumor was reached when pSLC was used at the dosage of 50 microg but not 100 or 200 microg. RT-PCR and real-time PCR revealed that both PD-L1 and PD-L2 genes were expressed in tumor and vicinal muscle tissues of tumor-bearing mice and the expression level was significantly increased if a higher dosage of pSLC was administered. We then constructed a eukaryotic expression plasmid (pPD-1A) that expresses the extracellular domain of murine PD-1 (sPD-1). sPD-1 could bind PD-1 ligands, block PD-Ls-PD-1 interactions, and enhance the cytotoxicity of tumor-specific CTL. Local gene transfer by injection of pPD-1A mediated antitumor effect and improved SLC-mediated antitumor immunity. The combined gene therapy with SLC plus sPD-1 did not induce remarkable autoimmune manifestations. Our findings provide a potent method of improving the antitumor effects of SLC and possibly other immunotherapeutic methods by local blockade of negative costimulatory molecules.

Animals↗
PubMed2004

[The pathogenesis of discogenic low back pain].

OBJECTIVE: To study the pathogenesis of the pain of discography and the discogenic low back pain. METHODS: 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, and 12 physiologically aging discs and 10 normal control discs were collected to investigate the morphologic features and innervation containing neuropeptides substance P (SP), neural filament (NF), and vasoactive-intestinal peptide (VIP). RESULTS: The distinct morphologic characteristic of the disc from the patient with discogenic low back pain was the formation of the strip zone of vascularized granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus in which there was one or several fissures. The structure of annulus fibrosus beyond the strip zone of granulation tissue was basically normal. The structures of the aging discs and the control discs showed the age-related changes. The innervation of SP, NF and VIP immunoreactive nerve fibers in the painful discs was more extensive compared with the aging discs and the control discs. The nerve in growth deep into annulus fibrosus and nucleus pulposus was observed mainly along the strip zone of granulation tissue in the painful discs. CONCLUSIONS: Findings indicate that the strip zone of granulation tissue with extensive innervation in the posterior part of the painful disc is the original site of the pain of discography and the discogenic low back pain. The strip zone of granulation tissue might originate from the injury and subsequent reparation of the margin of annulus fibrosus. The difference of the aging disc and painful disc which can not be differed each other on MRI is the formation of the strip zone of granulation tissue along tear histologically in posterior part of the painful disc.

Adult↗
PubMed2004

Preparation and property analysis of a hepatocyte targeting pH-sensitive liposome.

AIM: To develop a hepatocyte targeting pH-sensitive liposome for drug delivery based on active targeting technology mediated by asialoglycoprotein receptors. METHODS: Four types of targeting molecules with galactose residue were synthesized and mixed with pH-sensitive lipids DC-chol/DOPE to prepare liposome with integrated property of hepatocyte specificity and pH sensitivity. Liposome 18-gal was selected with the best transfection activity through cellular uptake experiment. Property analysis was made through experiments of competitive inhibition of receptors, red blood cell hemolysis, in vitro cytotoxicity test by MTS assay and mediation of inhibitory effects of antisense phosphorothioate ODN on gene expression, etc. RESULTS: Liposome 18-gal had the desired properties of hepatocyte specificity, pH sensitivity, low cytotoxicity, and high transfection efficiency. CONCLUSION: Liposome 18-gal can be further developed as a potential hepatocyte- targeting delivery system.

Cell Line, Tumor↗
PubMed2004

Hepatitis C virus (HCV) core antigen assay to detect ongoing HCV infection in thai injection drug users.

We evaluated a quantitative enzyme immunoassay (trak-C) for hepatitis C virus core antigen (HCV core Ag) by testing serum specimens from 820 injection drug users in Thailand with anti-HCV antibodies. The HCV genotypes in this population include genotypes 3 and 6, which have not been extensively tested with this assay. Among these specimens, 629 (76.7%) yielded positive results, with HCV core Ag concentrations predominantly spanning (35.7%) or above (58.2%) the measurable range of 1.5 to 100 pg/ml. To assess reproducibility, we retested 30 specimens representing six core Ag ranges; the mean coefficient of variation for each range was < or = 9.7% (highest for 1.5 to 25 pg/ml). We also tested 204 specimens of the 820-specimen set for HCV RNA: while 146 (71.6%) were core Ag positive, 168 (82.4%) had detectable HCV RNA, of which 96% were typeable as genotype 3 (39%), 1 (31%), or 6 (26%) by nested reverse transcription-PCR. Among RNA-positive specimens, 86.9% had core Ag; 94% of the RNA negatives were core Ag negative. While there was no apparent bias for detecting core Ag representing the tested genotypes, median quantified results were higher for types 1a and 6 than for genotype 3 (P = 0.01); similarly, the median core Ag concentration was higher in HCV-human immunodeficiency virus-coinfected subjects than in HCV-monoinfected subjects. Our results demonstrated a good correlation between core Ag and HCV RNA in this population with high frequencies of genotypes 3 and 6. Because most core Ag concentrations were greater than those in the measurable range, we recommend a 10-fold dilution of the specimen before quantification. Reproducibility, low technical requirements, and high throughput should make this assay useful for clinical or research monitoring of HCV levels during active infection.

Adolescent↗
PubMed2004

Accurate representation of the hepatitis C virus quasispecies in 5.2-kilobase amplicons.

Hepatitis C virus (HCV) exists as a swarm of genetically distinct but related variants, or a quasispecies, whose complexity and sequence evolution are critical to studies of viral pathogenesis. Because most studies of the HCV quasispecies have focused on a relatively small genomic segment, the first hypervariable region of the E2 gene, it is possible that viral complexity is occasionally underestimated (due to primer mismatch) and that sequence evolution is misperceived due to unrecognized covariation. This report describes a sensitive and reproducible method to amplify most of the HCV genome as a single 5.2-kb amplicon by using primers directed at relatively conserved genomic segments. Using 52 specimens obtained during acute infection over a range of viral RNA concentrations, the overall rate of successful amplification was 94% and varied in a concentration-dependent manner, with successful amplification in 26 of 26 (100%) specimens at greater than 10(5) IU/ml, 15 of 16 (94%) at 10(4) to 10(5) IU/ml, 6 of 7 (86%) at 10(3) to 10(4) IU/ml, and 2 of 3 (67%) at less than 10(3) IU/ml. Quasispecies complexity, determined by using this novel long-amplicon method followed by heteroduplex mobility assay combined with single-stranded conformational polymorphism (HDA+SSCP) analysis, was very high, even during acute HCV infection, when 10 to 21 (median, 16) different HDA+SSCP patterns were detected among 33 cDNA clones examined. Replicate analyses indicate that this diversity is not dominated by random errors generated during amplification. Therefore, the HCV quasispecies is highly complex even during acute infection and is accurately represented in amplicons representing more than half of the viral genome.

Amino Acid Sequence↗
PubMed2004

Cross-genotype immunity to hepatitis C virus.

Recent studies in humans and chimpanzees suggest that immunity can be induced to diminish the incidence of chronic hepatitis C virus (HCV) infection. However, the immunity that promotes viral recovery is poorly understood, and whether the breadth of this adaptive immunity is sufficient to overcome the substantial intergenotype antigenic diversity represents a final obstacle to demonstrating the feasibility of vaccine development. Here we demonstrate that recovery from a genotype 1 HCV infection protects chimpanzees against infection with representatives of other genotypes that exhibit up to 30% divergence at the amino acid level, including challenges with genotype 4, a mixture of genotypes 2 and 3, and a complex inoculum containing genotypes 1, 2, 3, and 4. In each instance, the level and duration of viremia were markedly reduced in comparison to the primary infection in the same animal. The data indicate that epitopes conserved between genotypes must play an essential role in immunity. The inocula used in the rechallenge studies induced typical primary infection profiles in naïve chimpanzees. Rechallenge infections were associated with rapid increases in the intrahepatic transcripts of interferon-stimulated genes, even in animals exhibiting apparent sterilizing immunity. Protective immunity was often associated with an early increase in gamma interferon transcripts in the liver and increases in intrahepatic transcripts of Mig, a T-cell chemokine that is a gamma interferon response gene. These studies are the first to show that cross-genotype immunity can be induced to HCV, demonstrating the feasibility of developing a vaccine protective against all HCV strains.

Animals↗
PubMed2004

Decryption of pure-position permutation algorithms.

Pure position permutation image encryption algorithms, commonly used as image encryption investigated in this work are unfortunately frail under known-text attack. In view of the weakness of pure position permutation algorithm, we put forward an effective decryption algorithm for all pure-position permutation algorithms. First, a summary of the pure position permutation image encryption algorithms is given by introducing the concept of ergodic matrices. Then, by using probability theory and algebraic principles, the decryption probability of pure-position permutation algorithms is verified theoretically; and then, by defining the operation system of fuzzy ergodic matrices, we improve a specific decryption algorithm. Finally, some simulation results are shown.

Algorithms↗
PubMed2004

[Eukaryotic expression and functional characterization of PD-1 extracellular domain].

The negative signal provided by interactions of costimulatory molecules, programmed death-1 (PD-1) and its ligands, PD-L1 (also B7-H1) and PD-L2 (also B7-DC), is involved in the mechanisms of tumor immune evasion. To block PD-Ls-PD-1 interactions by a soluble receptor of PD-1, we constructed a eukaryotic expression plasmid that expresses extracellular region (aa1-aa167) of murine PD-1 (pPD-1A) and, another version of pPD-1A, pPD-1B, carrying cDNAs encoding for both extracellular region of PD-1 and green fluorescent protein (GFP) reporter gene, which was inserted downstream of PD-1. Experiment of BHK cells transfected with pPD-1B determined that most expression product (sPD-1) in the cells was secreted out. FACS analysis revealed that sPD-1 was specific and bound efficiently to PD-1 ligands. Cytotoxicity assay showed that blocking PD-Ls on either tumor cells or spleen cells by sPD-1 mediated enhanced lysis of H22 cells by Hsp70-H22 peptides complexstimulated spleen cells. The constructed plasmid vector would provide a novel method of tumor gene therapy of blocking PD-Ls-PD-1 interactions by expression of soluble receptor of PD-1 in tumor sites, which could increase the antitumor activity.

Animals↗
PubMed2003

Directed random walks on directed percolation clusters.

The characteristics of directed random walks on directed percolation clusters are numerically studied. For two-dimensional clusters grown at the critical probability p(c), it is shown that the distance d of the directed random walkers from their most probable end point is determined by a probability distribution p(d) approximately d(-(1+w/nu)), where the values of w and nu are close to the values of the known exponents: w approximately 0.50 and nu approximately 0.63. This probability distribution is independent of the cluster's length t up to d values comparable to the cluster's width approximately t(nu). The results are shown to be consistent with a tree description of the directed percolation clusters.

Journal Article↗