• 제목/요약/키워드: gp120

검색결과 42건 처리시간 0.027초

수용성 CD-gp120 결합체의 면역화로 유도된 항 gp120 항체의 특성에 관한 연구 (Immunization with a soluble CD4-gp120 complex preferentially induces neutralizing anti-Human Immunodeficiency Virus Type lantibodies directed to conformation-dependent epitopes of gp120)

  • Kang, Chang-Yuil
    • 한국응용약물학회:학술대회논문집
    • /
    • 한국응용약물학회 1994년도 제2회 추계심포지움
    • /
    • pp.61-67
    • /
    • 1994
  • One fundamental problem in developing an AIDS vaccine is antigenic variation of HIV. Despite a substantial induced immune response in gp120-immunized monkeys and humans, high titers of V3-directed type specific neutralizing antibodies may not be sufficient to neutralize continuously emerging new isolates. Several studies analyzing anti-gp120 antibodies in HIV-infected individuals have clearly indicated that most broadly neutralizing antibodies are directed to conformation-dependent epitopes. Therefore, it seems important to evaluate the potential efficacy of candidate gp120 vaccines at inducing such antibodies, that might be potentially protective against multiple HIV strains. One concern in the development of any recombinant protein as a vaccine is its stability when mixed with an adjuvant. This could be a particularly important factor for recombinant gp120, given the conformational nature of its major, broadly neutralizing, epitopes. We hypothesized that gp120 complexed with recombinant CD4 could stabilize the conformation-dependent epitopes and effectively deliver these epitopes to the immune system. In this study, a soluble gp120-CD4 complex in Syntex Adjuvant Formulation was tested in mice to analyze the anti-gp120 antibody response. With the aim of defining the fine specificity and neutalizing activities of the immune response, 17Mabs were generated and characterized. The studies indicate that the gp120-CD4 complex elicits neutralizing anti-gp120 antibodies, most of which are directed to the conformation dependent epitopes.

  • PDF

Exploration of the Binding Mode of Indole Derivatives as Potent HIV-1 Inhibitors Using Molecular Docking Simulations

  • Balupuri, Anand;Cho, Seung Joo
    • 통합자연과학논문집
    • /
    • 제6권3호
    • /
    • pp.138-142
    • /
    • 2013
  • The HIV-1 envelope glycoprotein gp120 plays a vital role in the entry of the virus into the host cells. The crucial role of the glycoprotein suggests gp120 as potential drug target for the future antiviral therapies. Identification of the binding mode of small drug like compounds has been an important goal in drug design. In the current study we attempt to propose binding mode of indole derivatives in the binding pocket of gp120. These derivatives are reported to inhibit HIV-1 by acting as attachment inhibitors that bind to gp120 and prevent the gp120-CD4 interaction and thus inhibit the infectivity of HIV-1. To elucidate the molecular basis of the small molecules interactions to inhibit the glycoprotein function we employed the molecular docking simulation approach. This study provides insights to elucidate the binding pattern of indole-based gp120 inhibitors and may help in the rational design of novel HIV-1 inhibitors with improved potency.

The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro

  • Lu, Lin;Dong, Haixia;Liu, Guixiang;Yuan, Bin;Li, Yizhao;Liu, Huaxiang
    • Biomolecules & Therapeutics
    • /
    • 제22권6호
    • /
    • pp.532-539
    • /
    • 2014
  • Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (> $25{\mu}m$), whereas ddC mainly affected small diameter DRG neurons (${\leq}25{\mu}m$). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

포유동물 세포에서 Human Immunodeficiency Virus-1의 Oligomeric gp140 단백의 발현 및 특성 (Expression and Characterization of Human Immunodeficiency Virus-1 Oligomerized gp140 Protein in Mammalian Cells)

  • 김은옥;김은;김현수;신광순;김철중
    • 대한수의학회지
    • /
    • 제42권1호
    • /
    • pp.55-64
    • /
    • 2002
  • HIV-1의 envelope glycoprotein은 중화항체에 의한 체액성 면역반응의 중요한 target으로 surface glycoprotein인 gp120과 transmembrane glycoprotein인 gp41로 이루어져 있다. gp120과 gp41의 ectodomain으로 이루어진 gp140 유전자를 PCR의 방법으로 증폭하고 Semliki Forest virus(SFV) 유래 expression system을 이용하여 mammalian 세포에서 발현하였다. 발현된 gp140은 natural HIV-1에서와 같이 oligomer를 형성하였다. 발현된 gp140을 정제하여 BALB/c 마우스에 접종하여 항체가 형성되었음을 확인하였다.

Characterization of Binding Mode of the Heterobiaryl gp120 Inhibitor in HIV-1 Entry: A Molecular Docking and Dynamics Simulation Study

  • Gadhe, Changdev G.;Kothandan, Gugan;Cho, Seung Joo
    • Bulletin of the Korean Chemical Society
    • /
    • 제34권8호
    • /
    • pp.2466-2472
    • /
    • 2013
  • Human immunodeficiency virus type-1 (HIV-1) is a causative agent of Acquired immunodeficiency syndrome (AIDS), which has affected a large population of the world. Viral envelope glycoprotein (gp120) is an intrinsic protein for HIV-1 to enter into human host cells. Molecular docking guided molecular dynamics (MD) simulation was performed to explore the interaction mechanism of heterobiaryl derivative with gp120. MD simulation result of inhibitor-gp120 complex demonstrated stability. Our MD simulation results are consistent with most of the previous mutational and modeling studies. Inhibitor has an interaction with the CD4 binding region. Van der Waals interaction between inhibitor and Val255, Thr257, Asn425, Met426 and Trp427 were important. This preliminary MD model could be useful in exploiting heterobiaryl-gp120 interaction in greater detail, and will likely to shed lights for further utilization in the development of more potent inhibitors.

대장균에서 사람의 면역결핍 바이러스-1 epitopes 클로닝과 발현에 대한 연구 (Cloning and Expression of Human Immunodeficiency Virus-1 Epitopes in Escherichia coli)

  • 유향숙;장원희;박희동;현상원;남상욱;이영익
    • 미생물학회지
    • /
    • 제29권1호
    • /
    • pp.1-7
    • /
    • 1991
  • Human immunodeficiency virus type 1 (HIV-1) causes a deadly infectious disease, Acquired Immunodeficiency Syndrome (ADIS). As a first step to develop a reliable and fast diagnostic procedure for HIV-1 infection, we cloned various immunodominant epitopes of HIV-1 in bacterial expression vectors containing tac or trp promoter. While the protein level of direct expression of gp160 was low, trp E fused gp120, gp41 and p17-p24 were produced at high levels (15-30% of total bacterial proteins) in E. coli. Since gp120 and gp41 contain relatively conserved regions which can react with antibodies in the plasma from most of HIV-1 infected individuals, these expression clones were used for large preparations of HIV-1 antigens.

  • PDF

진핵세포에서 HSV-1 Envelope 변이 단백질의 발현 및 발현 단백질의 특성 연구 (Expression and Characterization of the Human Immunodeficiency Virus Type 1 Mutant Envelope Glycoproteins in Mammalian Cells)

  • 류지윤;박진서
    • 대한바이러스학회지
    • /
    • 제29권3호
    • /
    • pp.183-193
    • /
    • 1999
  • Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein is synthesized as a 160 KDa precursor, gp160, that is cleaved by a cellular protease to form the gp120 and gp41 subunits. Mammalian expression vectors were designed that are capable of efficient expression of various mutant envelope glycoproteins derived from a molecular clone of HIV-1. To construct these vectors, one type of mutation was made at the gp120-gp41 cleavage site by oligonucleotide-directed mutagenesis. And another mutation was made to change amino acids in the membrane spanning region of HIV-1 gp41 important for membrane anchorage. Next, these two mutations were combined to generate a vector to have double mutations in cleavage site and membrane-spanning region. These mutants were transiently expressed in mammalian cells. The effect of these mutations on envelope glycoprotein synthesis, proteolytic processing and secretion was determined. In addition, cell surface expression and ability of the glycoprotein to induce syncytium formation were examined. This study provides a mammalian expression system that is capable of efficient expression and secretion of soluble gp160.

  • PDF

Azasugar-Containing Phosphorothioate Oligonucleotide (AZPSON) DBM-2198 Inhibits Human Immunodeficiency Virus Type 1 (HIV-1) Replication by Blocking HIV-1 gp120 without Affecting the V3 Region

  • Lee, Jinjoo;Byeon, Se Eun;Jung, Ju Yeol;Kang, Myeong-Ho;Park, Yu-Jin;Jung, Kyeong-Eun;Bae, Yong-Soo
    • Molecules and Cells
    • /
    • 제38권2호
    • /
    • pp.122-129
    • /
    • 2015
  • DBM-2198, a six-membered azasugar nucleotide (6-AZN)-containing phosphorothioate (P = S) oligonucleotide (AZPSON), was described in our previous publication [Lee et al. (2005)] with regard to its antiviral activity against a broad spectrum of HIV-1 variants. This report describes the mechanisms underlying the anti-HIV-1 properties of DBM-2198. The LTR-mediated reporter assay indicated that the anti-HIV-1 activity of DBM-2198 is attributed to an extracellular mode of action rather than intracellular sequence-specific antisense activity. Nevertheless, the antiviral properties of DBM-2198 and other AZPSONs were highly restricted to HIV-1. Unlike other P = S oligonucleotides, DBM-2198 caused no host cell activation upon administration to cultures. HIV-1 that was pre-incubated with DBM-2198 did not show any infectivity towards host cells whereas host cells pre-incubated with DBM-2198 remained susceptible to HIV-1 infection, suggesting that DBM-2198 acts on the virus particle rather than cell surface molecules in the inhibition of HIV-1 infection. Competition assays for binding to HIV-1 envelope protein with anti-gp120 and anti-V3 antibodies revealed that DBM-2198 acts on the viral attachment site of HIV-1 gp120, but not on the V3 region. This report provides a better understanding of the antiviral mechanism of DBM-2198 and may contribute to the development of a potential therapeutic drug against a broad spectrum of HIV-1 variants.

실외 위치기반서비스 앱을 위한 건전지 절약 방법 (Methods of Energy Saving for Outdoor LBS Apps)

  • 임재걸
    • 한국컴퓨터정보학회:학술대회논문집
    • /
    • 한국컴퓨터정보학회 2017년도 제56차 하계학술대회논문집 25권2호
    • /
    • pp.119-120
    • /
    • 2017
  • 최신 스마트폰은 GPS(Global Positioning System) 신호를 이용하여 비교적 정확한 위치정보를 제공한다. 그래서 GPS를 이용한 다양한 실외용 위치기반서비스 앱이 개발되고 있다. 그러나 GPS를 이용하면 비교적 많은 건전지 에너지가 소모되어 사용자에게 큰 불편을 준다. 본 논문은 지도정보와 에너지 소모가 적은 센서를 이용하여 건전지를 절약하는 방안을 제안한다.

  • PDF