• Title/Summary/Keyword: Human Immunodeficiency virus

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Biochemical Properties of Second Site Mutation of Human Immunodeficiency Virus Integrase

  • Kim, Do-Jin;Oh, You-Take;Lee, Sang-Kwang;Shin, Cha-Gyun
    • BMB Reports
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    • v.32 no.6
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    • pp.599-604
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    • 1999
  • A highly conserved amino acid, glutamic acid (Glu), present at position 152 in the catalytic domain of the human immunodeficiency virus type 1 (HIV-1) integrase (IN) protein has been known to be critical for enzymatic function since substitution of Glu 152 with other residues results in a complete loss of enzymatic activities. In order to better understand the role of Glu 152 as a conserved residue in enzymatic action, intragenic second site mutations have been introduced around residue 152 of a mutant IN (E152A), and their biochemical properties were analyzed in terms of enzymatic activities. Disintegration activities were found to be significantly restored in several second site mutant INs, while integration activities were only recovered weakly. However, endonucleolytic activities were not discovered in all the mutant INs. These findings indicate that the second site mutations can partially restore that catalytic structure of the active site disturbed by the E152A mutation and lead to the regaining of integration and disintegration activities. In addition, it is also suggested that endonucleolytic activity requires a more accurate structure of the catalytic site than that for the integration and disintegration activities.

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A Human Immunodeficiency Virus Type 1 (HIV-1) Tat Cofactor Absent in Rodent Cells is a TAR-associated Factor

  • Lee, Im-soon;Shank, Peter R.
    • IMMUNE NETWORK
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    • v.2 no.3
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    • pp.150-157
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    • 2002
  • Background: Although Tat plays a role as a potent transactivator in the viral gene expression from the Human Immunodeficiency Virus type 1 long terminal repeat (HIV-1 LTR), it does not function efficiently in rodent cells implying the absence of a human specific factor essential for Tat-medicated transactivation in rodent cells. In previous experiments, we demonstrated that one of chimeric forms of TAR (transacting responsive element) of HIV-1 LTR compensated the restriction in rodent cells. Methods: To characterize the nature of the compensation, we tested the effects of several upstream binding factors of HIV-1 LTR by simple substitution, and also examined the role of the configuration of the upstream binding factor(s) indirectly by constructing spacing mutants that contained insertions between Sp1 and TATA box on Tat-mediated transactivation. Results: Human Sp1 had no effect whereas its associated factors displayed differential effects in human and rodent cells. In addition, none of the spacing mutants tested overcame the restriction in rodent cells. Rather, when the secondary structure of the chimeric HIV-1 TAR construct was destroyed, the compensation in rodent cells was disappeared. Interestingly, the proper interaction between Sp1 and TATA box binding proteins, which is essential for Tat-dependent transcription, was dispensable in rodent cells. Conclusion: This result suggests that the human-specific Tat cofactor acts to allow Tat to interact effectively in a ribonucleoprotein complex that includes Tat, cellular factors, and TAR RNA, rather than be associated with the HIV-1 LTR upstream DNA binding factors.

Peripheral Neuropathy Associated with Human Immunodeficiency Virus Infection (사람면역결핍바이러스 감염과 연관된 말초신경병증)

  • Lee, Min Hwan;Lim, Young-Min;Pyun, So Young;Kim, Jimin;Kim, Kwang-Kuk
    • Annals of Clinical Neurophysiology
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    • v.14 no.1
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    • pp.29-35
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    • 2012
  • Background: Peripheral neuropathy is the most frequent neurological complication in human immunodeficiency virus (HIV) infection, related with diverse etiologies including inflammation, opportunistic infection and side effects of medications. The purpose of the present study was to evaluate characteristics of HIV associated neuropathy according to the stage of HIV infection. Methods: In reviewing the medical records of HIV patients who underwent electrodiagnostic studies between 1997 and 2011, total 11 patients (all males; median age, 47 years; range, 28-71 years) with comorbid neuropathy were enrolled. Stage of HIV infection was categorized according to the Centers for Disease Control and Prevention (CDC) criteria. Classification of peripheral neuropathy was based on clinical and electrophysiological features. Results: Distal symmetric polyneuropathy was observed in 8 patients (72.7%), inflammatory demyelinating polyneuropathy in 2 patients (18.1%), and polyradiculopathy in 1 patient (9.1%). Median CD4+ T cell count was $123/mm^3$ (range, $8-540/mm^3$) and 7 patients (60%) had the most advanced HIV disease stage (CDC-C3). There was no neuropathy caused by CMV infection. Conclusions: Distal symmetric polyneuropathy was the most common type of neuropathy in HIV infection, but various forms of neuropathy such as inflammatory demyelinating polyneuropathy and polyradiculopathy were also present. HIV associated neuropathy is more frequently associated with advancing immunosuppression, although it can occur in all stages of HIV infection.

Effect of Korean Red Ginseng intake on the survival duration of human immunodeficiency virus type 1 patients

  • Cho, Young-Keol;Kim, Jung-Eun
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.222-226
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    • 2017
  • Background: Long-term ginseng intake can increase longevity in healthy individuals. Here, we examined if long-term treatment with Panax ginseng Meyer (Korean Red Ginseng, KRG) can also enhance survival duration (SD) in patients with human immunodeficiency virus type 1 (HIV-1) infection. Methods: We retrospectively analyzed 252 HIV-1 patients diagnosed from 1986 to 2013 prior to the initiation of antiretroviral therapy. Overall, 162 patients were treated with KRG ($3,947{\pm}4,943g$) for $86{\pm}63$ mo. The effects of KRG on SD were analyzed according to the KRG intake level and the length of the follow-up period. Results: There were significant correlations between the total amount of KRG and SD in the KRG intake group (r = 0.64, p < 0.0001) as well as between total amount of KRG and mean annual decrease in $CD4^+$ T-cell count in all 252 patients (r = -0.17, p < 0.01). The annual decrease in $CD4^+$ T-cell count (change in $cells/{\mu}L$) was significantly slower in KRG-treated patients than in patients receiving no KRG ($48{\pm}40$ vs. $106{\pm}162$; p < 0.001). The SD (in months) was also significantly longer in the KRG group than in the no-KRG group ($101{\pm}64$ vs. $59{\pm}40$, p < 0.01). Conclusion: KRG prolongs survival in HIV-1 patients, possibly by slowing the decrease in $CD4^+$ T-cell count.

Detection of Enteropathogens in Human Immunodeficiency Virus and Non-Human Immunodeficiency Virus-Infected Children with Acute Diarrhea in an Indonesian Tertiary Hospital Using Multiplex Real-Time Polymerase Chain Reaction

  • Dewi Wulandari;Rivaldi Febrian;Pramita Gayatri Dwipoerwantoro;Nia Kurniati
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.27 no.2
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    • pp.95-103
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    • 2024
  • Purpose: Diarrhea is one of the leading causes of mortality in children living in developing countries. The etiology of acute diarrhea in each healthcare center varies depending on place, time, and population. This study aimed to identify pathogen patterns in human immunodeficiency virus (HIV)-infected and non-HIV children suffering from acute diarrhea, using multiplex real time reverse transcriptase polymerase chain reaction (RT-PCR), in an Indonesian tertiary hospital. Methods: This cross-sectional study was conducted at Dr. Cipto Mangunkusumo National Hospital from March 2019 to April 2020. Results: The study showed that multiplex RT-PCR results were positive in 58.9% of the specimens, with more positive results in HIV-infected children than in non-HIV-infected children (70% vs. 54.7%). Altogether 72 enteropathogens were detected from all specimens. Enteropathogens in non-HIV children with acute diarrhea consisted of bacteria (70.6%) and viruses (29.4%) with a predominance of enteroaggregative Escherichia coli (25.4%), followed by Campylobacter spp. (11.8%), enteropathogenic E. coli (9.8%), Norovirus GII (7.8%), and Clostridium difficile (7.8%). Enteropathogens in HIV-infected children consisted of viruses (57.1%), bacteria (28.6%), and parasites (14.3%) comprising Norovirus GII (24%), Cryptosporidium spp. (14.3%), Campylobacter spp. (14.3%), Norovirus GI (14.3%), and Astrovirus (14.3%). Cryptosporidium spp. was the only parasite found in this study and was found only in HIV-infected children. In non-HIV children with acute diarrhea, most pathogens were invasive bacteria, while in HIV-infected children, more viral and parasite infections occurred, primarily caused by opportunistic pathogens. Conclusion: The pattern of enteropathogens can help clinicians determine further examinations and appropriate empirical antimicrobial therapy for the patient.

Introduction of Phylodynamics for Controlling the HIV/AIDS Epidemic in Korea

  • Bae, Jong-Myon
    • Journal of Preventive Medicine and Public Health
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    • v.51 no.6
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    • pp.326-328
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    • 2018
  • As over 1000 new cases of HIV/AIDS occur in Korea annually, preventive health programs against HIV/AIDS are urgently needed. Since phylodynamic studies have been suggested as a way to understand how infectious diseases are transmitted and evolve, phylodynamic inferences can be a useful tool for HIV/AIDS research. In particular, phylodynamic models are helpful for dating the origins of an epidemic and estimating its basic reproduction number. Thus, the introduction of phylodynamics would be a highly valuable step towards controlling the HIV/AIDS epidemic in Korea.

Inhibition of HIV-1 Pretense by Novel Dipeptide Isosteres Containing 2-Isoxazoline or $\alpha$-Hydroxy Ketomethylene

  • Kim, Do-Hyung;Park, Kwan-Yong;Chung, Yong-Jun;Kim, Byeang-Hyean
    • Biomolecules & Therapeutics
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    • v.2 no.2
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    • pp.155-160
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    • 1994
  • Human immunodeficiency virus type 1 (HIV-1) protease is essential for the replication of the virus and it is therefore an attractive target for antiviral drugs of HIV-1. Several dipeptide isosteres containing 2-isoxazoline or $\alpha$-hydroxy ketomethylene have been synthesized and their inhibitory effects on the HIV-1 protease examined. The enzymatically active HIV-1 protease was purified to homogeniety from E. coli transformed with a recombinant plasmid (pMAL-pro) containing the entire gene encoding the protease. The purified protease had the substrate specificity with Km value of 9.8$\mu$M when an undecapeptide His-Lys-Ala-Arg-Val-Leu-(p-nitro)Phe-Glu-Ala-Nle-Ser-amide was used as a substrate, and the products from the substrate after specific cleavage by HIV-1 protease were analyzed by HPLC. The synthetic compounds containing dipeptide isosteres showed specific inhibitory effects while a dipeptide isostere containing an isoxazoline ring inhibited the HIV-1 protease competitively with Ki value of 500 $\mu$M. Even if the inhibition effects of HIV-1 protease were not very high, these novel dipeptide isosteres can be used as key structural moieties for developing specific inhibitors of HIV-1 protease.

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Inactivation of Infectious Microorganisms by Disinfection and Sterilization Processes for Human Amniotic Membrane Grafts (이식을 위한 사람 양막의 소독 및 멸균공정에 의한 감염성 위해인자 불활화 효과)

  • Bae, Jung-Eun;Kim, Chan-Kyung;Kim, In-Seop
    • Korean Journal of Microbiology
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    • v.45 no.4
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    • pp.346-353
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    • 2009
  • Viral, bacterial, and fungal infection can be transmitted from donor to recipient via transplantation of human amniotic membrane. Therefore human amniotic membrane for transplantation should be disinfected and sterilized before use. The purpose of this study was to examine the efficacy of the disinfection process and sterilization processes used at human tissue bank in the inactivation of viruses, bacteria, and fungi. A variety of experimental model viruses, bacteria, and fungus for human pathogens, including the human immunodeficiency virus type 1 (HIV-1), bovine herpes virus (BHV), bovine viral diarrhoea virus (BVDV), hepatitis A virus (HAV), porcine parvovirus (PPV), Escherichia coli, Bacillus subtilis, and Candida albicans were all selected for this study. Enveloped viruses such as HIV-1, BHV, and BVDV were effectively inactivated to undetectable levels by 70% ethanol treatment, gamma irradiation process, and ethylene oxide (EO) gas sterilization process. Also non-enveloped viruses such as HAV and PPV were effectively inactivated to undetectable levels by gamma irradiation and EO gas treatment. However HAV and PPV showed high resistance to 70% ethanol treatment. E. coli and C. albicans were effectively inactivated to undetectable levels by 70% ethanol treatment, gamma irradiation process, and EO gas treatment. Also B. subtilis was effectively inactivated to undetectable levels by gamma irradiation process and EO gas treatment. However it showed high resistance to 70% ethanol treatment.