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81.
Increased temperature enhances the infectivity of human immunodeficiency virus type 1 (HIV-1), and this enhancement is inhibited by anti-CXCR4 peptide T140, implying that multiple-site binding is required to proceed to infection. Here, we tested whether the augmented infectivity induced by increased temperature could account for the heterogeneity of envelope molecules in the effectiveness of anti-V3 neutralization and anti-CXCR4 blocking. Pseudoviruses with the X4 envelope which were infectious at room temperature (RT) were more resistant to both anti-V3 neutralizing antibody 0.5beta and T140 than viruses infectious at 37 C and 40 C. Viruses infectious to cells treated with T140 were also resistant to 0.5beta. Based on the hypothesis that the HIV-1 viruses were carrying heterogeneity of functional and nonfunctional gp120 and required the formation of sufficient multiple-site binding of functional gp120 with receptors to proceed to infection, viruses with many functional gp120 which were infectious at RT and infectious to cells with reduced numbers of CXCR4 by T140 treatment were resistant to 0.5beta. Although viruses with many functional gp120 are a minority (less than 5%) of the infectious HIV-1 fraction, they are regarded as able to escape from neutralizing antibodies and coreceptor antagonists. 相似文献
82.
Kannan Tharakaraman Satoru Watanabe Kuan Rong Chan Jia Huan Vidya Subramanian Yok Hian Chionh Aditya Raguram Devin Quinlan Megan McBee Eugenia Z. Ong Esther S. Gan Hwee Cheng Tan Anu Tyagi Shashi Bhushan Julien Lescar Subhash G. Vasudevan Eng Eong Ooi Ram Sasisekharan 《Cell host & microbe》2018,23(5):618-627.e6
83.
Caroline S. Colley Bojana Popovic Sudharsan Sridharan Judit E. Debreczeni David Hargeaves Michael Fung 《MABS-AUSTIN》2018,10(1):104-117
C5a is a potent anaphylatoxin that modulates inflammation through the C5aR1 and C5aR2 receptors. The molecular interactions between C5a–C5aR1 receptor are well defined, whereas C5a–C5aR2 receptor interactions are poorly understood. Here, we describe the generation of a human antibody, MEDI7814, that neutralizes C5a and C5adesArg binding to the C5aR1 and C5aR2 receptors, without affecting complement–mediated bacterial cell killing. Unlike other anti–C5a mAbs described, this antibody has been shown to inhibit the effects of C5a by blocking C5a binding to both C5aR1 and C5aR2 receptors. The crystal structure of the antibody in complex with human C5a reveals a discontinuous epitope of 22 amino acids. This is the first time the epitope for an antibody that blocks C5aR1 and C5aR2 receptors has been described, and this work provides a basis for molecular studies aimed at further understanding the C5a–C5aR2 receptor interaction. MEDI7814 has therapeutic potential for the treatment of acute inflammatory conditions in which both C5a receptors may mediate inflammation, such as sepsis or renal ischemia–reperfusion injury. 相似文献
84.
Adriana Badarau Harald Rouha Stefan Malafa Michael B. Battles Laura Walker Nels Nielson 《MABS-AUSTIN》2016,8(7):1347-1360
LukGH (LukAB) is a potent leukocidin of Staphylococcus aureus that lyses human phagocytic cells and is thought to contribute to immune evasion. Unlike the other bi-component leukocidins of S. aureus, LukGH forms a heterodimer before binding to its receptor, CD11b expressed on professional phagocytic cells, and displays significant sequence variation. We employed a high diversity human IgG1 library presented on yeast cells to discover monoclonal antibodies (mAbs) neutralizing the cytolytic activity of LukGH. Recombinant LukG and LukH monomers or a LukGH dimer were used as capture antigens in the library selections. We found that mAbs identified with LukG or LukH as bait had no or very low toxin neutralization potency. In contrast, LukGH dimer-selected antibodies proved to be highly potent, and several mAbs were able to neutralize even the most divergent LukGH variants. Based on biolayer interferometry and mesoscale discovery, the high affinity antibody binding site on the LukGH complex was absent on the individual monomers, suggesting that it was generated upon formation of the LukG-LukH dimer. X-ray crystallography analysis of the complex between the LukGH dimer and the antigen-binding fragment of a very potent mAb (PDB code 5K59) indicated that the epitope is located in the predicted cell binding region (rim domain) of LukGH. The corresponding IgG inhibited the binding of LukGH dimer to target cells. Our data suggest that knowledge of the native conformation of target molecules is essential to generate high affinity and functional mAbs. 相似文献
85.
Ehsan Alirahimi Fatemeh Kazemi-Lomedasht Delavar Shahbazzadeh Mahdi Habibi-Anbouhi Mohammad Hosseininejad Chafi Nazli Sotoudeh Hajarossadat Ghaderi Serge Muyldermans Mahdi Behdani 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2955-2965
Background
An effective therapy against envenoming should be a priority in view of the high number scorpion stings and snakebites. Serum therapy is still widely applied to treat the envenomation victims; however this approach suffers from several shortcomings. The employment of monoclonal antibodies might be an outcome as these molecules are at the core of a variety of applications from protein structure determination to cancer treatment. The progress of activities in the twilight zone between genetic and antibody engineering have led to the development of a unique class of antibody fragments. These molecules possess several benefits and lack many possible disadvantages over classical antibodies. Within recombinant antibody formats, nanobodies or single domain antigen binding fragments derived from heavy chain only antibodies in camelids occupy a privileged position.Scope of review
In this paper we will briefly review the common methods of envenomation treatment and focus on details of various in vivo research activities that investigate the performance of recombinant, monoclonal nanobodies in venom neutralization.Major conclusions
Nanobodies bind to their cognate target with high specificity and affinity, they can be produced in large quantities from microbial expression systems and are very robust even when challenged with harsh environmental conditions. Upon administering, they rapidly distribute throughout the body and seem to be well tolerated in humans posing low immunogenicity.General significance
Scorpion and snake envenomation is a major issue in developing countries and nanobodies as a venom-neutralizing agent can be considered as a valuable and promising candidate in envenomation therapy. 相似文献86.
Sunil R. Vaidya Venkat S. Hamde Neelakshi S. Kumbhar Atul M. Walimbe 《Microbiology and immunology》2018,62(4):243-247
87.
出血热病毒株的分型和抗原性比较的进一步研究 总被引:2,自引:0,他引:2
本工作进一步对分离自不同来源的14株出血热病毒用空斑减少中和试验(PRNT)方法进行了分型。以不同株的家兔免疫血清对国际上血清Ⅰ型和Ⅱ型参考毒株进行试验,除分离自褐家鼠的K_(24)-株外,其余13株均可定为血清Ⅰ型或血清Ⅱ型用已知的Ⅰ型和Ⅱ型出血热高价免疫血清与K_(24)株进行中和试验,根据两型免疫血清的中和效价则可将K_(24)株定为血清Ⅱ型,但是K_(24)株免疫血清对6株Ⅰ型病毒和4株Ⅱ型病毒的中和效价几乎相同(相差≤2倍),表明K_(24)株是一株具有广谱中和抗原的出血热病毒。 相似文献
88.
89.
A Malley L Werner E Benjamini C Y Leung J Torres N Pangares S Shiigi M Axthelm 《Journal of medical primatology》1991,20(4):177-181
Synthetic envelope peptides of a simian retrovirus (SRV-2) were used to define both T- and B-cell epitopes of the envelope protein. The SRV-2 peptide 100-106 specifically blocks rhesus anti-SRV-2 neutralizing antibody activity, and a peptide 100-106 keyhole limpet hemocyanin conjugate induces a strong antipeptide antibody response. SRV-2 peptide 100-106 and 233-249 induces good T-cell proliferation of murine spleen cells immunized with the SRV-2 virus. Thus, SRV-2 envelope peptide 100-106 represents both a T- and B-cell epitope, and peptide 233-249 a T-cell epitope. 相似文献
90.
A water-insoluble polysaccharide (PCS3-II) extracted from sclerotium of Poria cocos was identified as a linear (1 → 3)-β-d-glucan by 13C NMR and gas chromatography. Aqueous 0.5 M NaOH/0.2 M urea was a good solvent for PCS3-II and the dependence of intrinsic viscosity ([η]) on weight-average molecular weight (Mw) was established in the Mw range from 7.68 × 104 to 5.14 × 105 to be [η] = 3.39 × 10?2 at 25 °C by using laser light scattering and viscometry. The chain conformation parameters of PCS3-II in the 0.5 M NaOH/0.2 M urea solution was 2.3 (± 0.3) nm for persistence length (q), 580 g mol?1 nm?1 for molar mass per unit contour length (ML), 0.8 (± 0.2) nm for the diameter of the chain (d) and 3.63 for limited characteristic ratio (C∞). The results revealed, for the first time, that PCS3-II existed as a flexible chain in 0.5 M NaOH/0.2 M urea aqueous solution. 相似文献