• Title/Summary/Keyword: human immunodeficiency virus type-1

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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
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    • v.38 no.2
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    • pp.122-129
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    • 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.

Development of Test System for Detection of Antibody to Human Immunodeficiency Virus Type 1 Subtype O (HIV-1 O형 항체 진단시료의 개발)

  • Cho, Young-Shik;Yu, Seung-Shin;Ha, Gun-Woo;Lee, Sang-Gook;Cho, Myung-Hwan;Shin, Hyung-Sik;Kim, Sun-Young
    • The Journal of Korean Society of Virology
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    • v.28 no.1
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    • pp.31-38
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    • 1998
  • In Korea, all domestic made test systems for detecting antibodies in HIV-1 contain the antigens from human immunodeficiency type 1 (HIV-1) subtype B. However, because HIV-1 subtype O is significantly different in amino acid sequences from all other subtypes of HIV-1, there has been a need for developing a test for detecting antibodies in subtype O. For this purpose, the entire nucleotide sequence corresponding to the extracellular domain of the transmembrane glycoprotein of HIV-1 subtype O was synthesized with consideration of Escherichia coli condon usage. Various regions of the extracellular domain were cloned into E. coli expression vectors and tested for levels of protein production. The nucleotide sequence, named ECTM, that can encode a 129 amino acid-long peptide, was found to be expressed at a high level in E. coli. The protein of approximately 17 kDa specifically reacted with sera from individuals infected with HIV-1 subtype O. The ECTM protein was purified to near homogeneity by the CM-T gel chromatography, using concentrated, denatured inclusion bodies. In Western blot analysis, the purified viral antigen reacted with sera from individuals infected with subtype O more efficiently than subtype B. The enzyme linked immunoabsorbent assay (ELISA) system was developed using the subtype O viral protein and compared with the commercially available kit lacking the antigens from subtype O. The ELISA kit containing the subtype O antigen ECTM alone efficiently reacted with sera from individuals infected with subtype O. The subtype O antigen-containing kit produced a positive absorbence even when sera were diluted 512-fold, suggesting a high sensitivity. The commercially available kit also reacted with subtype O sera, but produced a negative result at a dilution of 8-fold. Our results suggest that the currently available kit may not be able to efficiently detect subtype O sera and that the viral protein developed in this study may be added to the current system to maximize the detection of sera from individuals infected with subtype O.

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Changes in Differentially Expressed Genes in the Liver of Oryzias latipes by Binary Exposure to Carcinogenic Polycyclic Aromatic Hydrocarbons

  • Oh, Jeong-Hwan;Moon, Hyo-Bang;Choe, Eun-Sang
    • Korean Journal of Environmental Biology
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    • v.27 no.4
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    • pp.391-396
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    • 2009
  • The biological effects of carcinogenic polycyclic aromatic hydrocarbons (cPAHs) including benzo[a]pyrene (BaP), dibenzo[a,h]anthracene (DBA), benzo[a]anthracene (BaA), benzo[b] fluoranthene (BbF), benzo[k]fluoranthene (BkF), and indeno[1,2,3-c, d]pyrene (InP) on transcriptomic changes were determined in the liver of Oryzias latipes. Differentially expressed genes (DEGs) by binary exposure to cPAHs (BaP+BaA, BaP+BbF, BaP+BkF, BaP+DbA, BaP+InP) were screened by annealing control primers-based polymerase chain reaction followed by sequence analysis and BLAST searching. The results showed that four DEGs were commonly expressed by cPAHs and they were identified as ribosomal protein S4, coagulation factor II, elongation factor 1 beta, and a predicted protein similar to human immunodeficiency virus type I enhancer binding protein 3. This finding suggests that binary exposure to cPAHs interferes protein synthesis required for fundamental liver functions in fish.

Role of Curcuma longa, a traditional ayurvedic medicinal plant, in diabetes

  • Ponnusamy, Sudha;Zinjarde, Smita;Bhargava, Shobha;Kumara, Ameeta Ravi
    • CELLMED
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    • v.2 no.4
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    • pp.31.1-31.7
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    • 2012
  • Curcuma longa belongs to the family Zingiberaceae and can be found in the tropical and subtropical regions of the world. It is widely used in Asiatic countries, especially India and South East Asia where it is cultivated commercially as a condiment. Its rhizomes exhibit anti-inflammatory, anti-human immunodeficiency virus, anti-bacterial, antioxidant effects, nematocidal activities, antiproliferative and antiangiogenic activities and are of pharmaceutical importance. Another relevant medicinal property exhibited by it is antidiabetic property which is reviewed here. Studies on the efficacy of crude C.longa extracts against type 2 diabetes in murine models reveal that it demonstrates a hypoglycemic effect by lowering the blood glucose levels under in vivo conditions. Clinical studies have revealed the safety of curucmin (major principle component exhibiting pharmaceutical properties from C.longa) on humans but with very low bioavailability. In view of its effective hypoglycemic effect and its low bioavailability, further studies are needed for the characterization of the bioactive principles and formulating the development of C.longa extracts as a novel anti-diabetic therapeutic agent.

The High Resolution NMR Solution Structure of Monocyte Chemoattractant Protein-3

  • Kwon Do-Yoon;Lee Duck-Yeon;Sykes Brian D.;Kim Key-Sun
    • Journal of the Korean Magnetic Resonance Society
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    • v.9 no.2
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    • pp.74-92
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    • 2005
  • The high resolution solution structure of MCP-3 was determined using multinuclear, multidimensional NMR spectroscopy with an expressed and $^{13}C-\;and\;^{15}N-labeled$ protein. The MCP-3 has a typical chemokine fold including 3 anti-parallel $\beta-sheets$, and a C-terminal helix, but it exists as a monomer in solution under the conditions where the structure was determined (2 mM, pH 5.1 at $30^{\circ}C$). Based on the structure and the amino acid sequence compared to other chemokines we propose that Ile20 and Leu25 in MCP-3 play key roles in the formation of N-loop (residues between the $2^{nd}$ cysteine and the I sheet) which has been implicated as a determinant of chemokine specificity. Additional receptor binding surface is supplied by the 40s loop (residues between the 2 and the 3 sheet) and the binding interface of the acidic N-terminal region of chemokine receptor to MCP-3 would resemble the dimerization interface of CC type dimer.

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Inhibitory Effects of Campsis grandiflora on HIV-1 reverse Transcriptase, HIV-1 Protease and α-glucosidase (능소화 잎 및 줄기 추출물의 Human Immunodeficiency Virus Type I 억제활성)

  • Yu, Young-Beob
    • Korean Journal of Plant Resources
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    • v.25 no.2
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    • pp.169-175
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    • 2012
  • For the elucidation of action mechanism on anti-HIV of natural resources, the extracts of $Campsis$ $grandiflora$ were tested for their inhibitory effects on HIV-1 replication and its essential enzymes as the reverse transcriptase (RT), protease and ${\alpha}$-glucosidase. In the assay of HIV-1-infected human T-cell line, water extracts of stem inhibited the HIV-1-induced cytopathic effects with IC (inhibitory concentration) of 100 ${\mu}g$/ml. Moreover water extracts (100 ${\mu}g$/ml) of stem showed strong activity of 37.9% on anti-HIV-1 RT using Enzyme Linked Oligonucleotide Sorbent Assay (ELOSA) method. In the HIV-1 protease inhibition assay, methanol extracts of stem and leaf extract showed 33.6% and 31.5% inhibition of the enzyme activity to cleave an oligopeptide resembling one of the cleavage sites in the viral polyprotein which can only be processed by HIV-1 protease, but did not exhibited glucosidase inhibitory activities. From these results, it is suggested that the inhibition of the viral replication $in$ $vitro$ is due to the inhibition of reverse transcriptase by water extracts of stem of $Campsis$ $grandiflora$.

The Extracts of Kalopanax pictus Nakai. for Inhibitory Effects on HIV-1 and Its Essential Enzymes (Human Immunodeficiency Virus Type Ⅰ에 대한 음나무 추출물의 억제활성)

  • Yu Young Beob;Shim Bum Sang;Ahn Kyoo Seok;Choi Seung Hoon;Park Jong Cheol;Miyashiro H.;Hattori M.
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.4
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    • pp.1129-1133
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    • 2004
  • For the purpose of developing new anti-HIV agents from natural sources, the extracts of Kalopanax pictus were tested for their inhibitory effects on HIV-1 replication and its essential enzymes as the reverse transcriptase (RT). protease and α-glucosidase. In the assay of HIV-1-infected human T-cell line, water extracts of stem and leafstalk inhibited the HIV-1-induced cytopathic effects with Ie (inhibitory concentration) of 25 and 50㎍/㎖, respectively. Moreover water extracts (100㎍/㎖) of stem and leafstalk showed strong activity of 80% and 90% on anti-HIV-1 RT using Enzyme Linked Oligonucleotide Sorbent Assay (ELOSA) method. In the HIV-1 protease inhibition assay, aqueous stem extract inhibited the activity of the enzyme to cleave an oligopeptide, resembling one of the cleavage sites in the viral polyprotein which can only be processed by HIV-1 protease with 58%, but no glucosidase inhibitory activities. We found out this result, for these samples it is possible that the inhibition of the viral replication in vitro is due to the inhibition at least one of RT and protease. It would be of great interest to identify the compounds which are responsible for this inhibition, since all therapeutically useful agent up to date are RT, PR and α-glucosidase inhibitors.

Expression Profiles and Pathway Analysis in HEK 293 T Cells Overexpressing HIV-1 Tat and Nucleocapsid Using cDNA Microarray

  • Park, Seong-Eun;Lee, Min-Joo;Yang, Moon-Hee;Ahn, Ka-Young;Jang, Soo-In;Suh, Young-Ju;Myung, Hee-Joon;You, Ji-Chang;Park, Jong-Hoon
    • Journal of Microbiology and Biotechnology
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    • v.17 no.1
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    • pp.154-161
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    • 2007
  • Human immunodeficiency virus type 1 (HIV-1) infections are responsible for a substantial number of deaths annually and represent a significant threat to public health. According to the latest study, the Tat (Transactivator of transcription) protein is essential in transcription and replication of viral genes, and is among the early expression genes involved in the life cycle of HIV. The virion NC (nucleocapsid) plays an important role in early mRNA expression and contributes to the rapid viral replication that occurs during HIV-1 infection. Therefore, we attempted to elucidate the relationship between the Tat protein and nucleocapsid protein. In a comparison of two independently prepared and hybridized samples, flag NC overexpressed HEK 293T cells and pTat overexpressed HEK 293T cells, and hybridization showed the differences in expression in each case. Among the microarray results confirmed with real-time reverse transcriptase assay, twelve genes were identified to be involved according to their gene expression profiles. Of approximately 8,208 human genes that were analyzed, we monitored candidate genes that might have been related to NC and Tat genes from gene expression profiles. Additionally, the pathways could be viewed and analyzed through the use of Pathway Studio software. The pathways from the gene list were built and paths were found among the molecules/cell objects/processes by the curation method.

Subjectivity toward Death among HIV-Positive Men (HIV 감염인 남성의 죽음에 대한 주관성)

  • Lee, Eun-Ju
    • Journal of Hospice and Palliative Care
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    • v.17 no.3
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    • pp.142-150
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    • 2014
  • Purpose: This study was to identify the attitude of Korean HIV (Human Immunodeficiency Virus)-positive men toward death. Methods: A Q-methodology was performed with 20 HIV-positive male individuals. Participants were asked to select and answer questions among a set of 40 Q-statements using a 9-point scale. The collected data were analyzed using the PC QUANL program. Results: Participants' attitudes toward death were categorized into four types. Type I was characterized by respect for life, type II by reality orientation, type III by pain evasion and type IV religious beliefs. Conclusion: It is necessary to develop an assessment tool and an intervention program for HIV-positive individuals.

Screening of Some Plant Extracts for Inhibitory Effects on HIV-1 and Its Essential Enzymes (Human Immunodeficiency Virus Type I에 대한 수종 식물 추출물의 억제활성 검색)

  • Park, Jong-Cheol;Lee, Jong-Ho;Kim, Gyeong-Eup;Jo, Sung-Kee;Byun, Myung-Woo;Hirotsuku, Miyashiro;Masao, Hattori;Yu, Yeong-Beob
    • Korean Journal of Pharmacognosy
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    • v.29 no.4
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    • pp.338-346
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    • 1998
  • In order to elucidate the relationship between anti-HIV-1 enzyme activity and inhibition of HIV-1 replication by natural sources, extracts from some plants using the foods and oriental medicines were tested for inhibitory effects on the viral replication, reverse transcriptase (RT), protease and ${\alpha}-glucosidase$. In the anti-RT test, water extracts of Ficus carica (leaf), Houttuynia cordata (aerial part) and Ixeris tamagawaensis (aerial part) showed more than 79% inhitibion at a concentration of $100\;{\mu}g/ml$. The protease and ${\alpha}-glucosidase-inhibiting$ samples in the screening were water extract of Syringa dilatata (leaf) and methanol extract of Hibiscus syriacus (leaf and stem), which showed more than 40% inhibition at a concentration of $100\;{\mu}g/ml$. In the primary anti-HIV-1 test, water extracts of Equisetum arvense (aerial part), Hibiscus syriacus (leaf), Ixeris tamagawaensis (aerial part) and Pueraira thunbergiana (leaf) showed the potent inhibition against HIV-1 induced cytopathic effects.

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