• The Journal of Korean Society of Virology
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• v.28 no.1
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• pp.39-52
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• 1998

HIV-1 tat, a strong transactivator, is essential for the HIV-1 replication and AIDS progression. The Tat function is markedly inhibited by human anti-oncogene p53. This work was initiated to identify the p53-associated inhibitory mechanism on tat-mediated transactivation. Inhibitory function of p53 was confirmed by co-transfection of tat-expressing Jurkat cells with LTR-CAT plasmid, or H3T1 cells (LTR-CAT integrated HeLa cells) with different ratio of pSV-tat/pCDNA-p53 plasmids. Results from the direct protein-protein interaction between soluble p53 and tat, and yeast two-hybrid experiments showed that the co-suppression mechanism is unlikely to be due to the direct interaction. CAT activity was not affected by tat in Jurkat cells which were transfected with p53-promoter-CAT or p53-enhancer-CAT, suggesting that the tat-mediated p53 suppression is not directly associated with p53-promoter. Finally, we have tested protein kinase activity in p53-tranfected Jurkat cells, which might phosphorylate HIV-1 tat, resulting in inhibition of tat function. Some of our data lead us to assume that the p53-mediated tat inhibition is likely to be associated with p53-associated, signaling-mediated phosphorylation of tat, resulting in the dysfunction of tat. This study is now under investigation.

• Plant Resources
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• v.4 no.3
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• pp.196-199
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• 2001

Medicinal plants were screened for the inhibitory effects on human immunodeficiency virus type 1 pretense. Of the extracts tested, the strong inhibitory effects were observed in the acetone extracts of the pericarp of Camellia japonica. Camelliatannin H from the pericarp of C. japonica showed a potent inhibitory activity on HIV-1 pretense. Effects of the extract and compound from leaves of Zanthoxylum piperitum on the enzyme activities were investigated in the liver of bromobenzene-treated rats. The methanol extract and protocatechuic acid isolated from Z. pipetitum reduced the activity of aniline hydroxylase that increased by bromobenzene, while did not affect the activities of aminopyrin N-demethylase and glutathione S-transferase. The extract and protocatechuic acid recovered significantly the activity of epoxide hydrolase decreased by bromobenzene.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2001.11a
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• pp.68-73
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• 2001

Medicinal plants were screened for the inhibitory effects on human immunodeficiency virus type 1 pretense Of the extracts tested, the strong inhibitory effects were observed in the acetone extracts of the pericarp of Camellia japonica. Camelliatannin H from the pericarp of C. japonica showed a potent inhibitory activity on HIV- 1 pretense. Effects of the extract and compound from leaves of Zanthoxylum piperitum on the enzyme activities were investigated in the liver of bromobenzene-treated rats. The methanol extract and protocatechuic acid isolated from Z. piperitum reduced the activity of aniline hydroxylase that increased by bromobenzene, while did not affect the activities of aminopyrin N-demethylase and glutathione S-transferase The extract and protocatechuic acid recovered significantly the activity of epoxide hydrolase decreased by bromobenzene.

• Molecules and Cells
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• v.21 no.1
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• pp.7-20
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• 2006

The major event in human immunodeficiency virus type 1 (HIV-1) infection is the death of many cells related to host immune response. The demise of these cells is normally explained by cell suicide mechanism, apoptosis. Interestingly, the decrease in the number of immune cells, such as non-CD4+ cells as well as CD4+ T cells, in HIV infection usually occurs in uninfected bystander cells, not in directly infected cells. It has, therefore, been suggested that several soluble factors, including viral protein R (Vpr), are released from the infected cells and induce the death of bystander cells. Some studies show that Vpr interacts directly with adenine nucleotide translocator (ANT) to induce mitochondrial membrane permeabilization (MMP). The MMP results in release of some apoptogenic factors such as cytochrome-c (cyt-c) and apoptosis-inducing factor (AIF). Vpr also has indirect effect on mitochondria through enhancing the level of caspase-9 transcription and suppressing nuclear factor-kappa B (NF-${\kappa}B$). The involvement of p53 in Vpr-induced apoptosis remains to be studied. On the other hand, low level of Vpr expression has anti-apoptotic effect, whereas it's high level of expression induces apoptosis. Extracellular Vpr also exhibits cytotoxicity to uninfected bystander cells through apoptotic or necrotic mechanism. The facts that Vpr has cytotoxic effect on both infected cells and bystander cells, and that it exhibits both proand anti-apoptotic activity may explain its role in viral survival and disease progression.

• Korean Journal of Veterinary Research
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• v.40 no.3
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• pp.471-478
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• 2000

The pharmacokinetic properties of KR-V compounds, recently developed as new anti-HIV agents, were studied after i.v. and p.o. administration in rats. The concentrations of the KR-V series were determined in rat plasma using an high-performance liquid chromatography (HPLC)-UV detection system. Of the 19 KR-V compounds investigated in the present study, only KR-V 3, 10, 14, 16 and 18-1 showed oral bioavailability. The plasma concentration-time data could be adequately described by an one-compartment open model. In the i.v. kinetic study (10mg/kg), the CLt of KR-V 3, 10, 14 and 16 (>4L/hr/kg) were significantly higher than that of KR-V 18-1 (1.1 L/hr/kg). The AUC of KR-V 18-1 was greater ($8.97{\mu}g{\cdot}hr/ml$) than that of the other compounds, but the Vd (0.58 L/kg) was lower. In the p.o. kinetic study (50mg/kg), although the t-1/2 of KR-V 18-1 was shorter than that of the other compounds, the AUC ($3.659{\mu}g{\cdot}hr/ml)$ and $C_{max}(1.891{\mu}g/ml$) were markedly higher. In a seperated in vitro experiment, only KR-V 18-1, of the 5 compounds with bioavailibility, exhibits potent activity against HIV-1 mutant strains. Therefore, KR-V 18-1 is expected to become a new potent anti-AIDS drug candidate/lead compound.

• The Journal of Korean Society of Virology
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• v.30 no.1
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• pp.83-99
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• 2000

A defective HIV-1 helper virus DNA, pHyPC, was assembled by deleting the RNA packaging signal, env, nef and the 3'LTR sequences. HIV-1 like virus particles that carry the HIV-1 receptor, CD4 were generated by co expression of pHyPC and plasmid DNAs encoding different chimeric CD4 proteins. The CD4 particles, sharing the CD4 ectodomain, precisely fused to different membrane anchors. CD4(+) particles specifically bound to HIV-1 Env expressing cells, but any signs of infection into these cells were not detected. Binding was only partially blocked by either polyclonal anti-CD4 antibodies or by high concentrations of soluble CD4. Surprisingly, CD4(+) particles also adsorbed to HeLa, CHO, NIH3T3 and COS-7 cells in the absence of HIV-1 Env expression. Adsorption was comparable in strength and speed to the highly specific CD4-Env interaction. CD4(-) particles exhibited only background levels of binding. Cell binding was CD4. dependent, but it was independent of the cell type from which the CD4(+) particles originated. Interestingly, CD4-dependent/Env-independent binding was only found when CD4 was present on virus particles. This suggests that the micro-environment of CD4 on virus particles uniquely expose this new cell binding activity. Its high affinity could explain in part why infection of Env(+) cells by CD4(+) particles was not detected. Further experiments will be required to evaluate whether this strong membrane interaction could represent one step in the multiple-step viral entry process.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.630-644
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• 2003

A human Cu, Zn-superoxide dismutase (Cu, Zn-SOD) was fused with a Tat PTD of HIV-1 to produce a novel anti-aging ingredient, Tat-SOD for cosmeceuticals. Test of stability and evaluation of transduction efficacy and enzymatic activity suggest Tat-SOD is an effective active ingredient for anti-aging treatment.

• Bulletin of the Korean Chemical Society
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• v.34 no.3
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• pp.827-830
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• 2013

Investigation of an organic extract of the fruits Schisandra wilsoniana led to the isolation of two new highly oxygenated nortriterpenoids, named schilancidilactones V-W (1-2). Their structures were elucidated by spectroscopic evidence. Compounds 1-2 feature a double bond between C-7 and C-8 compared with related known nortriterpenoids isolated from the genus Schisandra. Compounds 1 and 2 were tested for their anti-HIV-1 activities and cytotoxicity. The results revealed that compounds 1 and 2 showed moderate anti-HIV-1 activities with $EC_{50}$ 3.05 and 2.87 ${\mu}g/mL$, respectively, and compound 1 showed high cytotoxicity against KB and MDA-MB-231 cell with $IC_{50}$ values of 3.18 and 5.22 ${\mu}M$, respectively.

• The Journal of the Korean Society for Microbiology
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• v.35 no.1
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• pp.9-18
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• 2000

Immunological mechanisms involving the release of inflammatory factors by HIV-1 infected microglia in the brain have been implicated in the pathogenesis of HIV dementia (HIVD). Since the regulation of matrix metalloproteinases (MMPs) activity can be influenced by variety of inflammatory mediators, this study was undertaken to look for a correlation between the MMP-9 release and the production of TNF-${\alpha}$ in response to HIV-1 p24 in the human monocyte cell line THP-1 as a model for microglia. First, it was shown that HIV-l core p24 antigen induced THP-1 to secrete MMP-9 in a dose response manner while it elicited a little effect on MMP-2 release in human astroglial cell line T98G. Next, it was found that p24 induced THP-1 to secrete TNF-${\alpha}$ without prior differentiation into macrophages by phorbol myristate acetate (PMA) treatment. Furthermore, anti-TNF-${\alpha}$ neutralizing antibodies significantly blocked p24-induced MMP-9 release in a dose dependent manner. Our data indicate that p24 antigen induces monocytic MMP-9 release by triggering up-regulation of TNF-${\alpha}$ secretion.

• Journal of Integrative Natural Science
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• v.8 no.3
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• pp.153-163
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• 2015

Racemic synthesis of novel 5',5'-difluoro-2'-methyl-apiose nucleoside phosphonic acid analogs was achieved as potent antiviral agents. Phosphonation was performed by direct displacement of triflate intermediate with diethyl (lithiodifluoromethyl) phosphonate to give the corresponding (${\alpha},{\alpha}$-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside analogs. An antiviral evaluation of the synthesized compounds against various viruses such as HIV, HSV-1, HSV-2 and HCMV revealed that the pyrimidine analogs (cytosine, uracil, and thymine) have weak anti-HIV or HCMV activity.