Abstract:
:Replacing the Pseudomonas exotoxin A (PE) cell binding domain with the human immunodeficiency virus (HIV) gp120 binding domain from CD4 yields a hybrid toxin (CD4-PE) with potential therapeutic use in treating acquired immunodeficiency syndrome (AIDS). To find the most therapeutically potent combination of CD4 and PE four different hybrid toxins composed of one [CD4(122)] or two [CD4(181)] Ig-like CD4 domains and sequences of PE where the binding domain was partially [PE(392)] or completely [PE(364)] removed were constructed and expressed in Escherichia coli. The number of CD4 domains determined the binding affinity to gp120 and in cell viability assays the window between specific and nonspecific cytotoxicity. The length of PE determined the potency of the drug. The optimal hybrid toxin was composed of two Ig-like domains of CD4 and PE(392). Investigation of the internalization mechanism of CD4-PE revealed that the hybrid toxin binds to target cells and is endocytosed within one hour. However, more than 6 hours are required for maximum translation inhibition. In contrast to PE which is inhibited by ammonium chloride treatment, cell toxicity of CD4-PE is not affected by ammonium chloride. Further investigations showed that the acid-induced hydrophobicity change which is required for membrane translocation is also observed with CD4-PE but at significantly higher pH than with PE.
journal_name
AIDS Res Hum Retrovirusesjournal_title
AIDS research and human retrovirusesauthors
Winkler G,Jakubowski A,Turner S,Liu T,Burrus B,McGray P,Heanue T,Rosa M,Griffiths BA,Wali Adoi
10.1089/aid.1991.7.393subject
Has Abstract,Author List Incompletepub_date
1991-04-01 00:00:00pages
393-401issue
4eissn
0889-2229issn
1931-8405journal_volume
7pub_type
杂志文章abstract::Benzylated peptides with a primary amino acid sequence corresponding to either human CD4(81-92) (#18), or chimpanzee CD4(81-92) (#18C), were equipotent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection of CD4+ cells and high-affinity binding of 125I-gp120 to CD4+ cells. The chimpanzee-based CD4(81-92...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1991.7.521
更新日期:1991-06-01 00:00:00
abstract::Stavudine (d4T) has been associated with lipoatrophy and hyperlactatemia. In recent studies, d4T has also been related to both hypercholesterolemia and hypertriglyceridemia. Replacing d4T with another nucleoside analogue such as abacavir (ABC) may reduce lactate levels and improve lipoatrophy in the long term. However...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2004.20.1289
更新日期:2004-12-01 00:00:00
abstract::The HIV-1 subtype distribution in 83 HIV-1-seropositive individuals living in Greece was investigated by using the heteroduplex mobility assay (HMA), DNA sequencing, and phylogenetic analysis. The results revealed that partial HIV-1 gp120 sequences from 71 (86%) patients were subtype B, 5 (6%) were subtype A, 4 were s...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究
doi:10.1089/aid.1998.14.685
更新日期:1998-05-20 00:00:00
abstract::Primary isolates of human immunodeficiency virus type 1 (HIV-1) were obtained by coculture of peripheral blood lymphocytes (PBLs) from HIV-1-infected people with PBLs from uninfected donors. These viral stocks tend to be resistant to neutralization/inactivation by soluble CD4 (sCD4). When these stocks were passed thro...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1995.11.335
更新日期:1995-03-01 00:00:00
abstract::The domain of HIV-2 Vpx previously shown to be important for virion incorporation has been mapped to residues 73--89. Mutational analysis of this domain was employed to further define the sequences important for incorporation into virus-like particles, using a vaccinia virus expression system. Deletion of residues 73-...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/08892220150217193
更新日期:2001-01-20 00:00:00
abstract::Jurkat cells stably expressing high levels of the HIV-1 Tat protein were generated after transfection with an Epstein-Barr virus-based episomal replicon and selection in hygromycin B. The Jurkat Tat transfectants exhibited a longer doubling time when compared to Jurkat cells or Jurkat cells transfected with the contro...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1995.11.443
更新日期:1995-04-01 00:00:00
abstract::Preexposure prophylaxis (PrEP) of HIV infection with tenofovir-containing regimens is effective, but plagued by poor adherence in some studies. Options for safe, effective, and acceptable PrEP products, especially for men and women at risk of HIV via receptive anal intercourse (RAI), are needed. We performed a randomi...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,随机对照试验
doi:10.1089/AID.2015.0086
更新日期:2015-11-01 00:00:00
abstract::Intense research into fundamental processes of human immunodeficiency syndrome type 1 (HIV-1) replication has yielded knowledge that in many aspects equals or exceeds that of the oncogenic retroviruses. The availability of sensitive virus detection methods has allowed a more thorough characterization of the biology of...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,评审
doi:10.1089/aid.1992.8.107
更新日期:1992-02-01 00:00:00
abstract::The efficacy, safety, and pharmacokinetics of three doses of tipranavir/ritonavir (TPV/r) in highly treatment-experienced human immunodeficiency virus (HIV)-1-infected patients with protease inhibitor (PI)-resistant isolates were evaluated. A 24-week multicenter, double-blind, randomized, dose-finding trial was conduc...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1089/aid.2006.0178
更新日期:2007-02-01 00:00:00
abstract::A new model system is delineated that will enable study of CD4 cofactors and gp120 binding proteins other than CD4. We have previously described a nontransformed rat fibroblast cell line that can efficiently produce HIV-1 upon transfection with an HIV-1 infectious clone, in contrast to other nonhuman mammalian cell li...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1996.12.1315
更新日期:1996-09-20 00:00:00
abstract::Non-B HIV-1 viruses are predominant in developing countries where access to antiretroviral drugs (ARVs) is progressively being intensified. It is important to obtain more data on the susceptibility of these viruses to available ARVs. CRF01_AE, CRF02_AG, and subtype C strains of HIV-1 obtained from untreated patients f...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.22.357
更新日期:2006-04-01 00:00:00
abstract::Lymphoid tissues are the focus of critical events in HIV pathogenesis. Persistent and high levels of virus production, extensive trapping of virus particles in germinal centers, and progressive degenerative changes in lymph node architecture are characteristics of progressive HIV-1 infection. Infiltrates of granzyme B...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299311330
更新日期:1999-03-01 00:00:00
abstract::HIV infection is associated with qualitative and functional immune deficiencies. It has been shown that the in vitro infection of CD4+ cells with HIV was associated with sustained elevation of cAMP and cGMP. In the present report the role of cAMP on HIV replication in MT-4 cells was investigated. The MT-4 cells were i...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1992.8.1255
更新日期:1992-07-01 00:00:00
abstract::A high incidence of decreased bone mineral density (BMD) has increasingly been associated with HIV infection. In this study mesenchymal stem cell (MSC) and human osteoblast (hOB) cell lines were treated with HIV tat, HIV rev, HIV p55-gag, HIV gp120 and HTLV env (100 ng/ml, 24 h). Cells were then analyzed for calcium d...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2007.0112
更新日期:2007-12-01 00:00:00
abstract::Women are now becoming the pivot of the epidemiological spread of HIV infection worldwide, especially in developing countries. Therefore, research to develop an efficient microbicide is now a priority for the prevention of HIV-1 acquisition in exposed women. However, recent disappointing failures in microbicide clinic...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2012.0049
更新日期:2012-11-01 00:00:00
abstract::Two cynomolgus macaques were infected with a genetically complex challenge stock of simian immunodeficiency virus (SIVmac251-32H). The polymerase chain reaction (PCR) was used to amplify the env gp41, rev, and nef overlapping coding sequences from provirus present in the blood of both animals at 1, 6, and 15 months po...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1993.9.133
更新日期:1993-02-01 00:00:00
abstract::Similarly to HIV-infected cells, recombinant HIV-1 glycoprotein 120 induces acid-labile interferon production in peripheral blood mononuclear cells from healthy donors. Acid lability of this interferon is due to the presence of both IFN-alpha and -gamma molecules. In fact, although not revealed by neutralization of an...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1993.9.957
更新日期:1993-10-01 00:00:00
abstract::HIV-1 infection is associated with vascular alterations. This is accompanied by an increased risk of cardiovascular diseases and Kaposi's sarcoma, an endothelial cell-derived tumor. We investigated the impact of maternal HIV-1 infection on phenotype and gene expression of endothelial cells in newborns. For this reason...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2005.21.940
更新日期:2005-11-01 00:00:00
abstract::HIV-specific CD4+ T cell responses, in particular to the HIV envelope antigen gp120, are often undetectable in the peripheral blood of HIV-infected individuals. The failure to detect these cells poses a significant impediment to studying the T cell populations that are considered to be essential for controlling HIV in...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922203769232593
更新日期:2003-09-01 00:00:00
abstract::The proportion of human immunodeficiency virus type 1 (HIV-1) among Vietnamese injecting drug users (IDUs) in Melbourne, Australia exceeds that of the background population. To investigate the molecular epidemiology of HIV-1 among this group, the C2-V4 region of the HIV-1 envelope was directly sequenced from 11 Vietna...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2004.20.1364
更新日期:2004-12-01 00:00:00
abstract::Epidemiological and experimental data suggest that both robust neutralizing antibodies and potent cellular responses play important roles in controlling primary HIV-1 infection. In this study we have investigated the induction of systemic and mucosal immune responses to HIV gp120 monomer immunogen administered intrana...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2007.0148
更新日期:2008-02-01 00:00:00
abstract::The relationship between adherence to highly active antiretroviral therapy (HAART) and RNA-HIV viral load outcomes has been extensively shown. Although there are different procedures for assessing treatment adherence, there is no ideal method. We present the SERAD (Self-Reported Adherence) questionnaire, a qualitative...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究
doi:10.1089/aid.2006.0120
更新日期:2007-10-01 00:00:00
abstract::The emergence of T cell-tropic, syncytium-inducing (T-tropic/SI) HIV-1 variants from the background of macrophage-tropic, non-syncytium-inducing (M-tropic/NSI) strains is associated with disease progression in infected individuals. HIV89.6 is a primary isolate with a transitional phenotype: like M-tropic strains it re...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1997.13.759
更新日期:1997-06-10 00:00:00
abstract::Cell activation is essential for HIV infection. CD4+ T lymphocyte activation allows virus replication and CD8+ T lymphocyte activation may contribute to pathogenesis. We combined hydroxyurea, a cytostatic drug that inhibits cell activation and proliferation, with two drugs that inhibit HIV (didanosine and indinavir), ...
journal_title:AIDS research and human retroviruses
pub_type: 临床试验,杂志文章
doi:10.1089/088922299310917
更新日期:1999-05-01 00:00:00
abstract::The transmembrane envelope (TM) protein gp41 of HIV-1 is an attractive target when designing a vaccine to induce neutralizing antibodies. A few broadly neutralizing antibodies (2F5, 4E10, and 10E8) that target conserved epitopes in the membrane proximal external region (MPER) of gp41 have been isolated from infected i...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2013.0191
更新日期:2014-05-01 00:00:00
abstract::Simian AIDS-related lymphomas (sARL) of cynomolgus monkeys infected with a simian immunodeficiency virus (SIVsm) were studied in relation to growth in severe combined immunodeficient (SCID) mice, karyotype abnormalities, and DNA sequence of the first noncoding region of the Bcl-6 gene. The tumors were diffuse large B ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922202753519160
更新日期:2002-03-20 00:00:00
abstract::Raltegravir, a novel HIV-1 integrase inhibitor, has superior efficacy with optimized background treatment (OBT) vs. placebo + OBT in treatment-experienced HIV-1 patients. This study assessed the long-term cost effectiveness of raltegravir from a Spanish National Healthcare System perspective. A cohort-state-transition...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2008.0254
更新日期:2009-07-01 00:00:00
abstract::We have investigated in utero human immunodeficiency virus type 1 (HIV-1) transmission by analyzing human fetal tissues for the presence of viral DNA by means of the polymerase chain reaction (PCR). Thirty three fetal samples: thymus, spleen, and peripheral mononuclear blood cells (PMBC) were obtained at abortion (16 ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1991.7.337
更新日期:1991-03-01 00:00:00
abstract::Sequences from the nef/LTR overlap region of the human immunodeficiency virus type 2 (HIV-2) genome were amplified from uncultured peripheral blood mononuclear cells (PBMCs) from 40 HIV-2-infected individuals in The Gambia, West Africa. Additional sequences from the plasma of three blood donors were also derived. Anal...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922201750063197
更新日期:2001-02-10 00:00:00
abstract::Changes in neutralizing antibody (NA) titers in stored sera collected over 5 years from 10 participants in the Multicenter AIDS Cohort Study (MACS) were evaluated. The participants were HIV-1 infected on enrollment in the MACS, and remained AIDS free during the 5-year study interval. Seven viruses derived from molecul...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究
doi:10.1089/aid.1998.14.939
更新日期:1998-07-20 00:00:00