scholarly journals The mechanism by which molecules containing the HIV gp41 core-binding motif HXXNPF inhibit HIV-1 envelope glycoprotein-mediated syncytium formation

2007 ◽  
Vol 403 (3) ◽  
pp. 565-571 ◽  
Author(s):  
Jing-He Huang ◽  
Heng-Wen Yang ◽  
Shuwen Liu ◽  
Jing Li ◽  
Shibo Jiang ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Critical Role ◽  
Syncytium Formation ◽  
Phage Clone ◽  
Fusion Process ◽  
Binding Motif ◽  
Active Core ◽  
Different Temperatures ◽  
Hiv 1

The HIV-1 gp41 (glycoprotein 41) core plays a critical role in fusion between the viral and target cell membranes. We previously identified a gp41 core-binding motif, HXXNPF, by screening the phage display peptide libraries. In the present study, we elucidated the mechanism of action of HXXNPF motif-containing molecules of different sizes, including the phage clone L7.8 (a selected positive phage clone), L7.8-g3p* (a 10–kDa fragment of the gene 3 protein) and JCH-4 (a peptide containing 13 residues of L7.8-g3p*), regarding their respective binding abilities to the six-helix bundle and inhibition on syncytium formation at different temperatures. We found that all of the HXXNPF motif-containing molecules could bind to the gp41 core, and that their binding sites may be located in the N-helix domain. L7.8-g3p* and JCH-4 effectively inhibited HIV-1 Env (envelope glycoprotein)-mediated syncytium formation at 37 °C, while the phage clone L7.8 showed no inhibition under the same conditions. However, at suboptimal temperature (31.5 °C), all of these HXXNPF motif-containing molecules were capable of inhibiting syncytium formation. These results suggest that these HXXNPF motif-containing molecules mainly bind to the gp41 core and stop the fusion process mediated by the fusion-active core, resulting in inhibition of HIV-1 fusion and entry. The HXXNPF motif-containing molecules may be used as probes for studying the role of the HIV-1 gp41 core in the late stage of the membrane-fusion process.

scholarly journals Genome-Wide Analysis of PR-1 Genes From Piper Nigrum Reveals Critical Role in Defense Response During Phytophthora Capsici Infection

2020 ◽  
Author(s):  
Divya Kattupalli ◽  
Asha Sriniva ◽  
Soniya E V
Keyword(s):  
Function Analysis ◽  
Phytophthora Capsici ◽  
Critical Role ◽  
Defense Responses ◽  
Regulatory Elements ◽  
Black Pepper ◽  
Piper Nigrum ◽  
Binding Motif ◽  
Genome Wide

Abstract Background: Black pepper is a prominent spice which is an indispensable ingredient in culinary and traditional medicine. Phytophthora capsici, the causative agent of foot rot disease causes drastic constraint in black pepper cultivation and productivity. To counterattack various biotic and abiotic stresses plants employ a broad array of mechanisms one such includes the accumulation of pathogenesis-related (PR) proteins. Several studies have reported the role of PR-1 proteins in triggering the plant defenses during plant-oomycete interaction.Results: Through the genome-wide survey, eleven PR-1 genes that belongs to a CAP superfamily protein with Caveolin-Binding Motif (CBM) and CAP-derived peptide (CAPE) were identified from P. nigrum. Despite the critical functional domains, PnPR1 homologs differ in their signal peptide motifs, and core amino acid sequence composition in the functional protein domains. The GO, biological function analysis reveals their role in defense responses and response to biotic stimulus whereas the KEGG functional annotation predicted their function in the plant-pathogen interactions. Furthermore, transcriptome-assisted FPKM analysis revealed PnPR-1 genes mapped to P. nigrum - P. capsici interaction pathway. The differentially expressed pathogen-responsive PR-1 gene was validated through qRT-PCR. Subsequent analysis revealed the structural details, phylogenetic relationships, conserved sequence motifs and critical cis-regulatory elements of PnPR-1 genes.Conclusion: This is the first genome-wide study that identified the role of PR-1 genes during P. nigrum - P. capsici interactions. The detailed in silico experimental analysis revealed the vital role of PnPR-1 genes in regulating the first layer of defense towards P. capsici infection in Panniyur-1 plants.

scholarly journals Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 76 ◽  
Author(s):  
Mitch Brinkkemper ◽  
Kwinten Sliepen
Keyword(s):  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Critical Role ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibodies ◽  
Viral Membrane ◽  
Immunodeficiency Virus ◽  
Hiv 1

The enormous sequence diversity between human immunodeficiency virus type 1 (HIV-1) strains poses a major roadblock for generating a broadly protective vaccine. Many experimental HIV-1 vaccine efforts are therefore aimed at eliciting broadly neutralizing antibodies (bNAbs) that are capable of neutralizing the majority of circulating HIV-1 strains. The envelope glycoprotein (Env) trimer on the viral membrane is the sole target of bNAbs and the key component of vaccination approaches aimed at eliciting bNAbs. Multimeric presentation of Env on nanoparticles often plays a critical role in these strategies. Here, we will discuss the different aspects of nanoparticles in Env vaccination, including recent insights in immunological processes underlying their perceived advantages, the different nanoparticle platforms and the various immunogenicity studies that employed nanoparticles to improve (neutralizing) antibody responses against Env.

scholarly journals Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1005 ◽  
Author(s):  
Jennifer L. Elliott ◽  
Sebla B. Kutluay
Keyword(s):  
Life Cycle ◽  
Viral Genome ◽  
Critical Role ◽  
Viral Rna ◽  
Target Cells ◽  
Host Chromosome ◽  
Virion Morphogenesis ◽  
Rna Genome ◽  
Hiv 1

The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small molecule inhibitors that now form key components of antiretroviral therapy regimens. Recent discoveries unveiled that IN has an under-studied yet equally vital second function in human immunodeficiency virus type 1 (HIV-1) replication. This involves IN binding to the viral RNA genome in virions, which is necessary for proper virion maturation and morphogenesis. Inhibition of IN binding to the viral RNA genome results in mislocalization of the viral genome inside the virus particle, and its premature exposure and degradation in target cells. The roles of IN in integration and virion morphogenesis share a number of common elements, including interaction with viral nucleic acids and assembly of higher-order IN multimers. Herein we describe these two functions of IN within the context of the HIV-1 life cycle, how IN binding to the viral genome is coordinated by the major structural protein, Gag, and discuss the value of targeting the second role of IN in virion morphogenesis.

scholarly journals A VH1-69 antibody lineage from an infected Chinese donor potently neutralizes HIV-1 by targeting the V3 glycan supersite

2020 ◽  
Vol 6 (38) ◽  
pp. eabb1328 ◽  
Author(s):  
Sonu Kumar ◽  
Bin Ju ◽  
Benjamin Shapero ◽  
Xiaohe Lin ◽  
Li Ren ◽  
...  
Keyword(s):  
Cell Sorting ◽  
Neutralizing Antibodies ◽  
Critical Role ◽  
Viral Escape ◽  
Germline Gene ◽  
Broadly Neutralizing Antibodies ◽  
Functional Studies ◽  
Single Genome ◽  
Hiv 1

An oligomannose patch around the V3 base of HIV-1 envelope glycoprotein (Env) is recognized by multiple classes of broadly neutralizing antibodies (bNAbs). Here, we investigated the bNAb response to the V3 glycan supersite in an HIV-1–infected Chinese donor by Env-specific single B cell sorting, structural and functional studies, and longitudinal analysis of antibody and virus repertoires. Monoclonal antibodies 438-B11 and 438-D5 were isolated that potently neutralize HIV-1 with moderate breadth, are encoded by the VH1-69 germline gene, and have a disulfide-linked long HCDR3 loop. Crystal structures of Env-bound and unbound antibodies revealed heavy chain–mediated recognition of the glycan supersite with a unique angle of approach and a critical role of the intra-HCDR3 disulfide. The mechanism of viral escape was examined via single-genome amplification/sequencing and glycan mutations around the N332 supersite. Our findings further emphasize the V3 glycan supersite as a prominent target for Env-based vaccine design.

Role of Glycosphingolipids in HIV-1 Entry: Requirement of Globotriosylceramide (Gb3) in CD4/CXCR4-dependent Fusion

1999 ◽  
Vol 19 (4) ◽  
pp. 317-325 ◽  
Author(s):  
Anu Puri ◽  
Peter Hug ◽  
Kristine Jernigan ◽  
Patrick Rose ◽  
Robert Blumenthal
Keyword(s):  
Structural Analysis ◽  
Cell Fusion ◽  
Envelope Glycoprotein ◽  
Human Erythrocyte ◽  
Head Group ◽  
Specific Interactions ◽  
Cd4 Cells ◽  
Fusion Site ◽  
Hiv 1

We have recently shown that addition of human erythrocyte glycosphingolipids (GSL) to non-human CD4+ or GSL-depleted human CD4+ cells rendered those cells susceptible to gp120-gp41-mediated cell fusion (Puri et al., BBRC, 1998). One GSL fraction (Fraction 3) isolated from human erythrocyte GSL mixture exhibited the highest recovery of fusion following incorporation into CD4+ non-human and GSL-depleted HeLa-CD4 cells (HeLa-CD4/GSL-). Structural analysis of Fraction 3 showed that this GSL had identical head group as the known GSL, Gal(α1→4)Gal(β1→4)Glc-Ceramide (Gb3) (Puri et al., PNAS, 1998). Here we report that presence of Gb3 in CD4+/CXCR4+ cells but not CD4+/CXCR4- cells allows fusion with HIV-1Lai-envelope glycoprotein expressing cells (TF228). Therefore, Gb3 functions in conjunction with HIV-1 co-receptor, CXCR4 to promote fusion. We propose that Gb3 functions by recruiting CD4 and/or CXCR4 at the fusion site through structurally specific interactions.

scholarly journals The critical role of human transcriptional repressor CTCF mRNA up-regulation in the induction of anti-HIV-1 responses in CD4+ T cells

2008 ◽  
Vol 117 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Yuchang Li ◽  
Guanhua Li ◽  
Anna Ivanova ◽  
Sagiv Aaron ◽  
Malgorzata Simm
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Critical Role ◽  
Transcriptional Repressor ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Role of Na+/H+ exchanger regulatory factor 1 in forward trafficking of the type IIa Na+-Pi cotransporter

2015 ◽  
Vol 309 (2) ◽  
pp. F109-F119 ◽  
Author(s):  
Corey J. Ketchem ◽  
Syed J. Khundmiri ◽  
Adam E. Gaweda ◽  
Rebecca Murray ◽  
Barbara J. Clark ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Critical Role ◽  
Mean Square Displacement ◽  
Active Movement ◽  
Binding Motif ◽  
Late Time ◽  
Cell Fractionation ◽  
Regulatory Factor ◽  
Ok Cells

Na+/H+ exchanger regulatory factor (NHERF1) plays a critical role in the renal transport of phosphate by binding to Na+-Pi cotransporter (NpT2a) in the proximal tubule. While the association between NpT2a and NHERF1 in the apical membrane is known, the role of NHERF1 to regulate the trafficking of NpT2a has not been studied. To address this question, we performed cell fractionation by sucrose gradient centrifugation in opossum kidney (OK) cells placed in low-Pi medium to stimulate forward trafficking of NpT2a. Immunoblot analysis demonstrated expression of NpT2a and NHERF1 in the endoplasmic reticulum (ER)/Golgi. Coimmunoprecipitation demonstrated a NpT2a-NHERF1 interaction in the ER/Golgi. Low-Pi medium for 4 and 8 h triggered a decrease in NHERF1 in the plasma membrane with a corresponding increase in the ER/Golgi. Time-lapse total internal reflection fluorescence imaging of OK cells placed in low-Pi medium, paired with particle tracking and mean square displacement analysis, indicated active directed movement of NHERF1 at early and late time points, whereas NpT2a showed active movement only at later times. Silence of NHERF1 in OK cells expressing green fluorescent protein (GFP)-NpT2a resulted in an intracellular accumulation of GFP-NpT2a. Transfection with GFP-labeled COOH-terminal (TRL) PDZ-binding motif deleted or wild-type NpT2a in OK cells followed by cell fractionation and immunoprecipitation confirmed that the interaction between NpT2a and NHERF1 was dependent on the TRL motif of NpT2a. We conclude that appropriate trafficking of NpT2a to the plasma membrane is dependent on the initial association between NpT2a and NHERF1 through the COOH-terminal TRL motif of NpT2a in the ER/Golgi and requires redistribution of NHERF1 to the ER/Golgi.

scholarly journals Critical role of PP2A-B56 family protein degradation in HIV-1 Vif mediated G2 cell cycle arrest

2020 ◽  
Vol 527 (1) ◽  
pp. 257-263
Author(s):  
Kayoko Nagata ◽  
Keisuke Shindo ◽  
Yusuke Matsui ◽  
Kotaro Shirakawa ◽  
Akifumi Takaori-Kondo
Keyword(s):  
Cell Cycle ◽  
Protein Degradation ◽  
Cell Cycle Arrest ◽  
Critical Role ◽  
Cycle Arrest ◽  
Family Protein ◽  
G2 Cell Cycle Arrest ◽  
Hiv 1

scholarly journals New Insights on the Versatile Role of the Cholesterol Binding Motif of the HIV-1 Glycoprotein Gp41

2014 ◽  
Vol 106 (2) ◽  
pp. 62a
Author(s):  
Roland Schwarzer ◽  
Andreas Herrmann ◽  
Ilya Levental ◽  
Andrea Gramatica
Keyword(s):  
Binding Motif ◽  
Glycoprotein Gp41 ◽  
Hiv 1 ◽  
Cholesterol Binding

scholarly journals Target of HIV-1 Envelope Glycoprotein gp120–Induced Hippocampal Neuron Damage: Role of Voltage-Gated K+ Channel Kv2.1

2015 ◽  
Vol 28 (9) ◽  
pp. 495-503 ◽  
Author(s):  
Qing Zhu ◽  
Xu Song ◽  
Jing Zhou ◽  
Yixin Wang ◽  
Jianxun Xia ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Hippocampal Neuron ◽  
K Channel ◽  
Voltage Gated ◽  
Envelope Glycoprotein Gp120 ◽  
Glycoprotein Gp120 ◽  
Neuron Damage ◽  
Hiv 1
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