Hepatitis C Virus Nonstructural Protein 5A Interacts with Immunomodulatory Kinase IKKε to Negatively Regulate Innate Antiviral Immunity.

Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulats beta interferon (IFN-β) promoter activity.

Characteristics of recent HIV infection among individuals newly diagnosed as HIV-positive in South Korea (2008-2015).

Most HIV-positive individuals diagnosed in Korea are infected through sexual contact, with the time of HIV infection therefore often being unknown. The aim of this study was to investigate the characteristics of diagnosed patients near the time of HIV seroconversion to establish useful HIV intervention strategies. Cross-sectional study.

Hepatocyte Growth Factor-Dependent Antiviral Activity of Activated cdc42-Associated Kinase 1 Against Hepatitis B Virus.

Activated cdc42-associated kinase 1 (ACK1) is a well-known non-receptor tyrosine kinase that regulates cell proliferation and growth through activation of cellular signaling pathways, including mitogen-activated protein kinase (MAPK). However, the anti-HBV activity of ACK1 has not been elucidated. This study aimed to investigate the role of ACK1 in the HBV life cycle and the mechanism underlying the anti-HBV activity of ACK1.

Transcriptome Analysis Identifies Altered Biological Processes and Novel Markers in Human Immunodeficiency Virus-1 Long-Term Non-Progressors.

Background: The latent reservoir of Human Immunodificiency Virus-1 (HIV-1) has been a major barrier to the complete eradication of HIV-1 and the development of HIV therapy. Long-term non-progressors (LTNPs) are a rare group of patients with HIV-1 who can spontaneously control HIV-1 replication without antiretroviral therapy. Transcriptome analysis is necessary to predict the pathways involved in the natural control of HIV-1, elucidate the mechanisms involved in LTNPs, and find biomarkers for HIV-1 reservoir therapy.

Enhanced disease progression due to persistent HPV-16/58 infections in Korean women: a systematic review and the Korea HPV cohort study.

Background: Persistent human papillomavirus (HPV) infection is a key factor for the development and progression of cervical cancer. We sought to identify the type-specific HPV prevalence by cervical cytology and assess disease progression risk based on high-risk persistent HPV infection in South Korea.

Methods: To investigate the HPV prevalence by Pap results, we searched seven literature databases without any language or date restrictions until July 17, 2019.

Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of a present pandemic, infects human lung alveolar type 2 (hAT2) cells. Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study.

Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19.

The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect.

Identification of Aristolactam Derivatives That Act as Inhibitors of Human Immunodeficiency Virus Type 1 Infection and Replication by Targeting Tat-Mediated Viral Transcription.

Despite the success of antiretroviral therapy (ART), efforts to develop new classes of antiviral agents have been hampered by the emergence of drug resistance. Dibenzo-indole-bearing aristolactams are compounds that have been isolated from various plants species and which show several clinically relevant effects, including anti-inflammatory, antiplatelet, and anti-mycobacterial actions. However, the effect of these compounds on human immunodeficiency virus type 1 (HIV-1) infection has not yet been studied.

Antiviral activity of interferon-stimulated gene 20, as a putative repressor binding to hepatitis B virus enhancer II and core promoter.

Background And Aim: Interferon-stimulated gene 20 (ISG20) is an interferon-inducible exonuclease that inhibits the replication of several RNA viruses. In patients with chronic hepatitis B, ISG20 expression is related to the interferon-α treatment response. However, the molecular mechanism of ISG20-mediated anti-hepatitis B virus (HBV) activity is unclear.

Identification of novel compounds against Tat-mediated human immunodeficiency virus-1 transcription by high-throughput functional screening assay.

Trans-activator (Tat)-mediated human immunodeficiency virus type 1 (HIV-1) transcription is essential for the replication of HIV-1 and is considered a potent therapeutic target for HIV-1 inhibition. In this study, the Library of Pharmacologically Active Compounds (LOPAC) was screened using our dual-reporter screening system for repositioning as Tat-inhibitory compounds. Consequently, two compounds were found to be potent, with low cytotoxicity.

Phylogenetic transmission clusters among newly diagnosed antiretroviral drug-naïve patients with human immunodeficiency virus-1 in Korea: A study from 1999 to 2012.

Population-level phylogenetic patterns reflect both transmission dynamics and genetic changes, which accumulate because of selection or drift. In this study, we determined whether a longitudinally sampled dataset derived from human immunodeficiency virus (HIV)-1-infected individuals over a 14-year period (1999-2012) could shed light on the transmission processes involved in the initiation of the HIV-1 epidemic in Korea. In total, 927 sequences were acquired from 1999 to 2012; each sequence was acquired from an individual patient who had not received treatment.

Impact of HIV-1 subtype and Korean Red Ginseng on AIDS progression: comparison of subtype B and subtype D.

Background: To date, no study has described disease progression in Asian patients infected with HIV-1 subtype D.

Methods: To determine whether the disease progression differs in patients infected with subtypes D and B prior to starting combination antiretroviral therapy, the annual decline (AD) in CD4 T cell counts over 96 ± 59 months was retrospectively analyzed in 163 patients and compared in subtypes D and B based on the gene.

Results: CD4 T cell AD was significantly higher in the six subtype D-infected patients than in the 157 subtype B-infected patients irrespective of Korean Red Ginseng (KRG) treatment ( < 0.

Identification of a quadruple mutation that confers tenofovir resistance in chronic hepatitis B patients.

Background & Aims: Tenofovir disoproxil fumarate (TDF) is one the most potent nucleot(s)ide analogues for treating chronic hepatitis B virus (HBV) infection. Phenotypic resistance caused by genotypic resistance to TDF has not been reported. This study aimed to characterize HBV mutations that confer tenofovir resistance.

Selection of biomarkers for HIV-1 latency by integrated analysis.

A major obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1) is its ability to establish latent infection. To find novel biomarkers associated with the mechanism of HIV-1 latent infection, we identified 70 candidate genes in HIV-1 latently infected cells through the integrated analysis in a previous study. It is important to select more effective biomarkers among 70 candidates and to verify the possibility of selected biomarkers for HIV-1 latency.

Development of a dual reporter screening assay for distinguishing the inhibition of HIV Tat-mediated transcription from off-target effects.

Human immunodeficiency virus (HIV) encodes a transcription trans-activator (Tat) with an essential role in the transcriptional elongation of viral RNA based on the viral promoter long terminal repeat (LTR). Tat-mediated transcription is conserved and can be distinguished from host transcription, so it is a therapeutic target for combating HIV replication. Traditional screening assays for Tat-mediated transcriptional inhibitors are based on the biochemical properties of Tat and transactivation-responsive RNA.

Identification of novel genes associated with HIV-1 latency by analysis of histone modifications.

Background: A reservoir of HIV-1 is a major obstacle in eliminating HIV-1 in patients because it can reactivate in stopping antiretroviral therapy (ART). Histone modifications, such as acetylation and methylation, play a critical role in the organization of chromatin domains and the up- or downregulation of gene expression. Although many studies have reported that an epigenetic mechanism is strongly involved in the maintenance of HIV-1 transcriptional latency, neither the epigenetic control of viral replication nor how HIV-1 latency is maintained is not fully understood.

Synergistic reactivation of latent HIV-1 provirus by PKA activator dibutyryl-cAMP in combination with an HDAC inhibitor.

HIV-1 reservoirs remain a major barrier to HIV-1 eradication. Although combination antiretroviral therapy (cART) can successfully reduce viral replication, it cannot reactivate HIV-1 provirus in this reservoir. Therefore, HIV-1 provirus reactivation strategies by cell activation or epigenetic modification are proposed for the eradication of HIV-1 reservoirs.

Highly activated p53 contributes to selectively increased apoptosis of latently HIV-1 infected cells upon treatment of anticancer drugs.

Background: Despite the successful inhibition of human immunodeficiency virus type 1 (HIV-1) replication by combination antiretroviral therapy, cells latently infected with HIV-1 remaining in patients are a major obstacle for eradication of HIV-1 infection. The tumor suppressor factor p53 is activated by HIV-1 infection, and restricts HIV-1 replication. However, a therapeutic strategy based on p53 activity has not been considered for elimination of latently infected cells.

Functional characteristics of the natural polymorphisms of HIV-1 gp41 in HIV-1 isolates from enfuvirtide-naïve Korean patients.

HIV-1 gp41 plays a key role in viral entry. The insertion of Thr at position 4 and Met/Val/Phe substitutions at position 7 are frequently observed in the fusion peptide (FP) motif of gp41 without major enfuvirtide resistance associated with mutation in heptad repeats 1/2 (HR1/2) of HIV-1 isolates from Korean patients. Here, the influence of these mutations on their biological function was evaluated by employing HIV-1 variants with mutant FPs as shown previously and with recombinant HIV-1 using the env genes of 20 HIV-1 isolates from Korean patients.

A Simple Mouse Model for the Study of Human Immunodeficiency Virus.

Humanized mouse models derived from immune-deficient mice have been the primary tool for studies of human infectious viruses, such as human immunodeficiency virus (HIV). However, the current protocol for constructing humanized mice requires elaborate procedures and complicated techniques, limiting the supply of such mice for viral studies. Here, we report a convenient method for constructing a simple HIV-1 mouse model.

Modification of AxSYM Human Immunodeficiency Virus Assay to Identify Recent Human Immunodeficiency Virus Infections in Korean Human Immunodeficiency Virus-Positive Individuals.

Objectives: To estimate human immunodeficiency virus (HIV) incidence using HIV avidity assays in Korea, we established a serological testing method to differentiate recent HIV infections from long-standing ones.

Methods: We adopted two incidence assays, the BED HIV-1 incidence test (Calypte Biomedical) and an HIV avidity assay (using Abbott AxSYM HIV Antigen/Antibody Combo), and performed them on Korean HIV samples obtained from 81 HIV seroconverters (n = 193), 135 HIV-positive samples, and three HIV commercial incidence panels (PRB965, PRB933, and PRB601 from SeaCare). To determine the most optimal concentration of the chaotropic agent (Guanidine) and the cutoff value for the avidity assay, we evaluated the sensitivity and specificity of the assay at different concentration levels.

Impaired IL-2 expression in latent HIV-1 infection.

Regarding the T cell function in HIV-1 infection, activation of T cells is enhanced in acutely HIV-1-infected T cells upon stimuli. However, T cell immune responses underlying the activation of T cell receptor (TCR) signaling molecules and interleukin (IL)-2 production in latently HIV-1-infected cells are poorly understood. The expression and activation of TCR components and its downstream molecules in acutely and latently HIV-1-infected T cells were compared using quantitative reverse transcription polymerase chain reaction (RT-PCR) for mRNA expression and enzyme-linked immunosorbent assay (ELISA) for levels of IL-2 in phytohemagglutinin M (PHA-M).

Hypermethylation of the tumor-suppressor cell adhesion molecule 1 in human papillomavirus-transformed cervical carcinoma cells.

Epigenetic modification at CpG islands located on the promoter regions of tumor-suppressor genes has been associated with tumor development in many human cancers. Our study showed that the cell adhesion molecule 1 (CADM1) is downregulated in human papillomavirus (HPV)-infected cervical cancer cell lines via its hypermethylation and demethylation using 5-aza-2'-deoxycyticine (5-aza-dC) restored the expression of CADM1 protein. Overexpression of CADM1 inhibited cell proliferation.

Interferon-inducible protein 10 (IP-10) is associated with viremia of early HIV-1 infection in Korean patients.

Cytokines/chemokines play key roles in modulating disease progression in human immunodeficiency virus (HIV) infection. Although it is known that early HIV-1 infection is associated with increased production of proinflammatory cytokines, the relationship between cytokine levels and HIV-1 pathogenesis is not clear. The concentrations of 18 cytokines/chemokines in 30 HIV-1 negative and 208 HIV-1 positive plasma samples from Korean patients were measured by the Luminex system.