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Liping Wang

Publications and source records attributed to Liping Wang.

50 records · Page 3Linked to original sources
PubMed2004

Characterization of the outer domain of the gp120 glycoprotein from human immunodeficiency virus type 1.

The core of the gp120 glycoprotein from human immunodeficiency virus type 1 (HIV-1) is comprised of three major structural domains: the outer domain, the inner domain, and the bridging sheet. The outer domain is exposed on the HIV-1 envelope glycoprotein trimer and contains binding surfaces for neutralizing antibodies such as 2G12, immunoglobulin G1b12, and anti-V3 antibodies. We expressed the outer domain of HIV-1(YU2) gp120 as an independent protein, termed OD1. OD1 efficiently bound 2G12 and a large number of anti-V3 antibodies, indicating its structural integrity. Immunochemical studies with OD1 indicated that antibody responses against the outer domain of the HIV-1 gp120 envelope glycoprotein are rare in HIV-1-infected human sera that potently neutralize the virus. Surprisingly, such outer-domain-directed antibody responses are commonly elicited by immunization with recombinant monomeric gp120. Immunization with soluble, stabilized HIV-1 envelope glycoprotein trimers elicited antibody responses that more closely resembled those in the sera of HIV-1-infected individuals. These results underscore the qualitatively different humoral immune responses elicited during natural infection and after gp120 vaccination and help to explain the failure of gp120 as an effective vaccine.

AIDS Vaccines↗
PubMed2004

[Research of bone bridge-like on plasma sprayed HA coating].

Bone formation on hydroxyapatite (HA) coating in the presence of gaps is important for clinical application. Pure Ti and hydroxyapatite coated by plasma sprayed samples were implanted in dog respectively. The implants were surrounded by gaps of 2 mm, and the follow-up period was 12 weeks. Histological examination and histomorphometry revealed that gaps could be bridged by bone provided the hydroxyapatite coating was applied, and that pure Ti implants were surrounded by fibrous tissue with no bone contact at all.

Animals↗
PubMed2003

Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains.

Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the beta 19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies.

Antibodies, Monoclonal↗
PubMed2003

Structure-based, targeted deglycosylation of HIV-1 gp120 and effects on neutralization sensitivity and antibody recognition.

The human immunodeficiency virus (HIV-1) exterior envelope glycoprotein, gp120, mediates receptor binding and is the major target for neutralizing antibodies. Primary HIV-1 isolates are characteristically more resistant to broadly neutralizing antibodies, although the structural basis for this resistance remains obscure. Most broadly neutralizing antibodies are directed against functionally conserved gp120 regions involved in binding to either the primary virus receptor, CD4, or the viral coreceptor molecules that normally function as chemokine receptors. These antibodies are known as CD4 binding site (CD4BS) and CD4-induced (CD4i) antibodies, respectively. Inspection of the gp120 crystal structure reveals that although the receptor-binding regions lack glycosylation, sugar moieties lie proximal to both receptor-binding sites on gp120 and thus in proximity to both the CD4BS and the CD4i epitopes. In this study, guided by the X-ray crystal structure of gp120, we deleted four N-linked glycosylation sites that flank the receptor-binding regions. We examined the effects of selected changes on the sensitivity of two prototypic HIV-1 primary isolates to neutralization by antibodies. Surprisingly, removal of a single N-linked glycosylation site at the base of the gp120 third variable region (V3 loop) increased the sensitivity of the primary viruses to neutralization by CD4BS antibodies. Envelope glycoprotein oligomers on the cell surface derived from the V3 glycan-deficient virus were better recognized by a CD4BS antibody and a V3 loop antibody than were the wild-type glycoproteins. Absence of all four glycosylation sites rendered a primary isolate sensitive to CD4i antibody-mediated neutralization. Thus, carbohydrates that flank receptor-binding regions on gp120 protect primary HIV-1 isolates from antibody-mediated neutralization.

Binding Sites↗
PubMed2003

Expression patterns of odorant-binding proteins in antennae of the moth Manduca sexta.

Monoclonal antibodies (MAbs) were generated to six recombinant proteins (odorant-binding proteins; OBPs) of Manduca sexta. The specificity of each MAb was demonstrated by labeling six immunoblots, each of which contained samples of all six recombinant OBPs. The expression patterns of the six OBPs could be grouped into three classes: (1) one (GOBP1) was expressed in sensilla located throughout each annulus; (2) two (ABPX and ABP2) were expressed in the long sensilla trichoidea bordering a zone that was arranged as an arch on the periphery of each annulus; (3) three (PBP2, PBP3, and GOBP2) were expressed in shorter sensilla occupying a wedge-shaped mid-annular zone of each annulus. In female antennae, sensilla expressing these OBPs were intermixed, and the distinct zonation observed in the male antenna was absent. In males, PBP2 was co-expressed in exactly the same cells of the mid-annular zone as those expressing PBP3 and most of the same cells expressing GOBP2, although its expression overlapped with no or only a few sensilla expressing OBPs of class 1 (GOBP1) or class 2 (ABPX, ABP2). This overlap of expression or lack of overlap between PBP2 and the other OBPs for male antennae was mirrored in female antennae. In view of the restricted spatial expression of OBPs within an annulus and the diversity of possible dimeric combinations of OBPs that arises from the co-expression of multiple OBPs in a given sensillum, OBPs could contribute to the specificity of the olfactory responses of insects.

Animals↗
PubMed2003

Tyrosine sulfation of human antibodies contributes to recognition of the CCR5 binding region of HIV-1 gp120.

Sulfated tyrosines at the amino terminus of the principal HIV-1 coreceptor CCR5 play a critical role in its ability to bind the HIV-1 envelope glycoprotein gp120 and mediate HIV-1 infection. Here, we show that a number of human antibodies directed against gp120 are tyrosine sulfated at their antigen binding sites. Like that of CCR5, antibody association with gp120 is dependent on sulfate moieties, enhanced by CD4, and inhibited by sulfated CCR5-derived peptides. Most of these antibodies preferentially associate with gp120 molecules of CCR5-utilizing (R5) isolates and neutralize primary R5 isolates more efficiently than laboratory-adapted isolates. These studies identify a distinct subset of CD4-induced HIV-1 neutralizing antibodies that closely emulate CCR5 and demonstrate that tyrosine sulfation can contribute to the potency and diversity of the human humoral response.

Amino Acid Sequence↗
PubMed2003

Activation of the signal transducer and activator of transcription 1 signaling pathway in thymocytes from HIV-1-infected human thymus.

OBJECTIVE: To identify HIV-induced host factors in the severe combined immunodeficient (SCID)-hu Thy/Liv mouse that may contribute to HIV pathogenesis in the thymus. DESIGN: To identify genes specifically altered by HIV-1 infection using the cDNA microarray assay, SCID-hu Thy/Liv organs derived from the same donors were used. Therefore, no genetic variations existed between HIV and mock-infected samples. In addition, the 12-14 day post-infection timepoint was chosen because no significant thymocyte depletion was detected in HIV-infected Thy/Liv organs, so mRNA from the same cell types could be compared. METHODS: Using SCID-hu Thy/Liv mice constructed from the same donor tissues, we analysed the expression of 9183 host genes in response to HIV infection with cDNA microarrays. Expression of selected genes with more than threefold induction was confirmed by measuring RNA (reverse transcriptase-polymerase chain reaction; RT-PCR) and proteins. RESULTS: HIV-1 (JD or NL4-3) infection of the SCID-hu Thy/Liv mouse led to more than threefold induction of 19 genes, 12 of which were IFN-inducible and six were unknown EST clones. We confirmed induction by RT-PCR and protein blots. Both signal transducer and activator of transcription (STAT)1 and STAT2 proteins were induced, and STAT1 was also activated by phosphorylation at the Tyr701 and Ser727 sites in human thymus infected with HIV-JD or NL4-3. Treatment of human fetal thymus organ culture or human thymocytes with recombinant HIV-1 gp120 proteins also led to induction or activation of STAT1. CONCLUSION: HIV-1 infection of the thymus led to activation of the STAT1 signaling pathway in thymocytes, which may contribute to HIV-1 pathogenesis in the thymus.

Animals↗
PubMed2003

Porcine pancreatic icosapeptide as a marker of graft survival and rejection in xenotransplantation.

The previous study showed that it is possible to monitor the viability of xenografted fetal pig pancrease in the first 3 weeks after transplantation in a normoglycemic immunoincompetent mouse [1]. This is achieved by measuring serum levels of porcine pancreatic icosapeptide (PI) in the host using a specific immunoassay. PI is secreted from the pancreatic polypeptide (PP) cell, the first mature endocrine cell of the fetal pig pancreas. Insufficient insulin is produced by the graft at this time to use it as a marker of graft viability. We have now examined the usefulness of PI to monitor graft survival in diabetic immunoincompetent mice and in immunosuppressed mice. Fetal porcine pancreatic tissue was transplanted beneath the renal capsule of streptozotocin-diabetic non-obese diabetic severe combined immunodeficient mice (NOD-SCID) and BALB/c mice given cyclosporin (CsA) for 21 or 10 days, respectively. Blood and grafts were analyzed periodically over 15 and 3 weeks, respectively, for porcine PI and C-peptide/insulin. In the diabetic mice, porcine PI was detected in sera up to 2 weeks following transplantation and was absent thereafter. Serum porcine C-peptide was detectable at 3 weeks and reached maximum levels at 12 to 15 weeks. PI content of the grafts was highest at day 4 and 3 weeks and lowest from 9 weeks onwards while insulin levels in the graft were highest from 9 weeks onwards. In BALB/c mice immunosuppressed with CsA, serum PI was detectable for 21 days. In the mice given CsA only for 10 days, serum PI was detectable for that time, but not on day 14 although PI was detectable in the graft. In mice given no CsA, PI was undetectable in serum at any time although PI was present in the graft at day 4. The presence of porcine PI in sera is a marker of graft survival of fetal porcine pancreatic tissue in diabetic immunocompetent mice in the first 2 weeks after transplantation. Its absence in immunosuppressed mice in this period is an early indicator of graft rejection.

Animals↗
PubMed2003

[Effects of Alexandrium tamarense and Prorocentrum donghaiense on rotifer Brachionus plicatilis population].

The effects of Prorocentrum donghaiense and Alexandrium sp., causative species of harmful algal bloom of East China Sea in May 2002, on rotifer Brachionus plicatilis population were studied in the laboratory. The results showed that Alexandrium tamarense (ATHK) had a lethal effect on B. plicatilis and the 48hLC50 was about 1300 cell.ml-1. The toxin comparison of different fractions showed that the algal culture and re-suspended algal cells had the adverse effects, and the alga at earlier growth phases showed a stronger impact, indicating that the inhibitory effect was related with the activity of the living algal cells. P. donghaiense at high densities (4 x 10(4), 5 x 10(4) and 10 x 10(4) cell.ml-1) had an adverse effect on B. plicatilis population, while at low densities (1 x 10(4), 2 x 10(4) and 3 x 10(4) cell.ml-1), the alga could be used as food for rotifer population. When the two algae were mixed, the lethal effect of A. tamarense could be decreased by P. donghaiense. The results indicated that the above HAB event could affect the micro-zooplankton population in the occurrence area of East China Sea.

Animals↗
PubMed2003

[Research advance in effects of harmful algal bloom species on zooplankton].

The research on the effects of harmful algal bloom (HAB) algae on zooplankton has been drawn more and more attention. This paper summarized the adverse effects of HAB algae on zooplankton, which included reduced survival, inhibited growth, reduced fecundity of female, fertilization failure of eggs or hatching failure of zygote, inhibited embryo development, naupliar abnormal development or abnormality, inhibited grazing and changed behavior of zooplankton, etc. The main intoxication ways included decreased utilization of food, physiology impairment, damaged cell membrane, reduced gamete quality, and inhibited mitotic and embryo development by phycotoxins or exudations released by algae. Additionally, the lack of full nutrition, especially of polyunsaturated fatty acids in some algal species cells could also affect zooplankton growth and reproduction.

Animals↗
PubMed2002

HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites.

The ability of human immunodeficiency virus (HIV-1) to persist and cause AIDS is dependent on its avoidance of antibody-mediated neutralization. The virus elicits abundant, envelope-directed antibodies that have little neutralization capacity. This lack of neutralization is paradoxical, given the functional conservation and exposure of receptor-binding sites on the gp120 envelope glycoprotein, which are larger than the typical antibody footprint and should therefore be accessible for antibody binding. Because gp120-receptor interactions involve conformational reorganization, we measured the entropies of binding for 20 gp120-reactive antibodies. Here we show that recognition by receptor-binding-site antibodies induces conformational change. Correlation with neutralization potency and analysis of receptor-antibody thermodynamic cycles suggested a receptor-binding-site 'conformational masking' mechanism of neutralization escape. To understand how such an escape mechanism would be compatible with virus-receptor interactions, we tested a soluble dodecameric receptor molecule and found that it neutralized primary HIV-1 isolates with great potency, showing that simultaneous binding of viral envelope glycoproteins by multiple receptors creates sufficient avidity to compensate for such masking. Because this solution is available for cell-surface receptors but not for most antibodies, conformational masking enables HIV-1 to maintain receptor binding and simultaneously to resist neutralization.

Antibody Affinity↗
PubMed2002

Mutagenic stabilization and/or disruption of a CD4-bound state reveals distinct conformations of the human immunodeficiency virus type 1 gp120 envelope glycoprotein.

The human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein is conformationally flexible. Upon binding to the host cell receptor CD4, gp120 assumes a conformation that is recognized by the second receptor, CCR5 and/or CXCR4, and by the CD4-induced (CD4i) antibodies. Guided by the X-ray crystal structure of a gp120-CD4-CD4i antibody complex, we introduced changes into gp120 that were designed to stabilize or disrupt this conformation. One mutant, 375 S/W, in which the tryptophan indole group is predicted to occupy the Phe 43 cavity in the gp120 interior, apparently favors a gp120 conformation closer to that of the CD4-bound state. The 375 S/W mutant was recognized as well as or better than wild-type gp120 by CD4 and CD4i antibodies, and the large decrease in entropy observed when wild-type gp120 bound CD4 was reduced for the 375 S/W mutant. The recognition of the 375 S/W mutant by CD4BS antibodies, which are directed against the CD4-binding region of gp120, was markedly reduced compared with that of the wild-type gp120. Compared with the wild-type virus, viruses with the 375 S/W envelope glycoproteins were resistant to neutralization by IgG1b12, a CD4BS antibody, were slightly more sensitive to soluble CD4 neutralization and were neutralized more efficiently by the 2G12 antibody. Another mutant, 423 I/P, in which the gp120 bridging sheet was disrupted, did not bind CD4, CCR5, or CD4i antibodies, even though recognition by CD4BS antibodies was efficient. These results indicate that CD4BS antibodies recognize conformations of gp120 different from that recognized by CD4 and CD4i antibodies.

CD4 Antigens↗
PubMed2002

[Influence of 4-aminopyridine on voltage-activated K(+) current and cell proliferation in small cell lung cancer].

OBJECTIVE: To study the inhibition of voltage-activated K(+) conductance and cell proliferation by 4-aminopyridine (4-AP) in the human small-cell lung cancer (SCLC). METHODS: Inhibition of voltage-activated K(+) current by 4-AP through the whole-cell patch-clamp technique in SCLC cell line was studied. The influence on the cell-cycle by 4-AP was observed by flow cytometry to identify the in vitro inhibition by 4-AP to the cell proliferation of the SCLC cell line. RESULTS: Exposure of the tumor cells to 5 mmol/L 4-AP reduced the peak outward K(+) current (evoked by a depolarization to +80 mV) from 1.22 +/- 0.11 nA (n = 30) to 0.59 +/- 0.10 nA (n = 28). Flow cytometry results showed that cell population accumulated in the G(0)/G(1) phase and a significantly reduced proportion in the S phase and G(1)/G(2) phase cells after having been exposed to 4-AP for three days. Incubation of the SCLC cells with 0.1, 5, 10, 15, 20 mmol/L 4-AP resulted in a concentration-and time-dependent reduction in the number of viable cells as compared with the control. CONCLUSION: The voltage-activated K(+) channels expressed by SCLC play an important role in SCLC cell proliferation. The proliferation of the SCLC cells is inhibited by K(+) channel antagonists.

4-Aminopyridine↗