• Title/Summary/Keyword: Host genome

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Functional Implications in Apoptosis by Interferon Inducible Gene Product 1-8D, the Binding Protein to Adenovirus Preterminal Protein

  • Joung, In-Sil;Angeletti, Peter C.;Engler, Jeffrey A.
    • Journal of Microbiology
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    • v.41 no.4
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    • pp.295-299
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    • 2003
  • Adenovirus (Ad) precursor to the terminal protein (pTP) plays an essential roles in the viral DNA replication. Ad pTP serves as a primer for the synthesis of a new DNA strand during the initiation step of replication. In addition, Ad pTP forms organized spherical replication foci on the nuclear matrix (NM) and anchors the viral genome to the NM. Here we identified the interferon inducible gene product 1-8D (Inid) as a pTP binding protein by using a two-hybrid screen of a HeLa cDNA library. Of the clones obtained in this assay, nine were identical to the Inid, a 13-kDa polypeptide that shares homology with genes 1-8U and Leu-13/9-27, most of which have little known functions. The entire open reading frame (ORF) of Inid was cloned into the tetracycline inducible expression vector in order to determine the biological functions related with adenoviral infection. When Inid was introduced to the cells along with adenoviruses, fifty to sixty percent of Ad-infected cells expressing Inid had rounded morphology, which was suggestive of apoptosis. Results from the terminal deoxynucleotidyl transferase (TdT) and DNA fragmentation assays confirmed that Inid induces apoptosis in Ad-infected or in uninfected cells. The Inid binding to pTP may target the cell for apoptotic destruction as a host defense mechanism against the viral infection.

Molecular Approaches to Taenia asiatica

  • Jeon, Hyeong-Kyu;Eom, Keeseon S.
    • Parasites, Hosts and Diseases
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    • v.51 no.1
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    • pp.1-8
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    • 2013
  • Taenia solium, T. saginata, and T. asiatica are taeniid tapeworms that cause taeniasis in humans and cysticercosis in intermediate host animals. Taeniases remain an important public health concerns in the world. Molecular diagnostic methods using PCR assays have been developed for rapid and accurate detection of human infecting taeniid tapeworms, including the use of sequence-specific DNA probes, PCR-RFLP, and multiplex PCR. More recently, DNA diagnosis using PCR based on histopathological specimens such as 10% formalin-fixed paraffin-embedded and stained sections mounted on slides has been applied to cestode infections. The mitochondrial gene sequence is believed to be a very useful molecular marker for not only studying evolutionary relationships among distantly related taxa, but also for investigating the phylo-biogeography of closely related species. The complete sequence of the human Taenia tapeworms mitochondrial genomes were determined, and its organization and structure were compared to other human-tropic Taenia tapeworms for which complete mitochondrial sequence data were available. The multiplex PCR assay with the Ta4978F, Ts5058F, Tso7421F, and Rev7915 primers will be useful for differential diagnosis, molecular characterization, and epidemiological surveys of human Taenia tapeworms.

Generation of Full-Length Infectious cDNA Clones of Middle East Respiratory Syndrome Coronavirus

  • Lee, Jeong Yoon;Bae, Sojung;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • v.29 no.6
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    • pp.999-1007
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    • 2019
  • Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 and related infection cases have been reported in over 20 countries. Roughly 10,000 human cases have so far been reported in total with fatality rates at up to 40%. The majority of cases have occurred in Saudi Arabia with mostly sporadic outbreaks outside the country except for the one in South Korea in 2015. The Korean MERS-CoV strain was isolated from the second Korean patient and its genome was fully sequenced and deposited. To develop virus-specific protective and therapeutic agents against the Korean isolate and to investigate molecular determinants of virus-host interactions, it is of paramount importance to generate its full-length cDNA. Here we report that two full-length cDNAs from a Korean patient-isolated MERS-CoV strain were generated by a combination of conventional cloning techniques and efficient Gibson assembly reactions. The full-length cDNAs were validated by restriction analysis and their sequence was verified by Sanger method. The resulting cDNA was efficiently transcribed in vitro and the T7 promoter-driven expression was robust. The resulting reverse genetic system will add to the published list of MERS-CoV cDNAs and facilitate the development of Korean isolate-specific antiviral measures.

Wheat Blast in Bangladesh: The Current Situation and Future Impacts

  • Islam, M. Tofazzal;Kim, Kwang-Hyung;Choi, Jaehyuk
    • The Plant Pathology Journal
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    • v.35 no.1
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    • pp.1-10
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    • 2019
  • Wheat blast occurred in Bangladesh for the first time in Asia in 2016. It is caused by a fungal pathogen, Magnaporthe oryzae Triticum (MoT) pathotype. In this review, we focused on the current status of the wheat blast in regard to host, pathogen, and environment. Despite the many efforts to control the disease, it expanded to neighboring regions including India, the world's second largest wheat producer. However, the disease occurrence has definitely decreased in quantity, because of many farmers chose to grow alternate crops according to the government's directions. Bangladesh government planned to introduce blast resistant cultivars but knowledges about genetics of resistance is limited. The genome analyses of the pathogen population revealed that the isolates caused wheat blast in Bangladesh are genetically close to a South American lineage of Magnaporthe oryzae. Understanding the genomes of virulent strains would be important to find target resistance genes for wheat breeding. Although the drier winter weather in Bangladesh was not favorable for development of wheat blast before, recent global warming and climate change are posing an increasing risk of disease development. Bangladesh outbreak in 2016 was likely to be facilitated by an extraordinary warm and humid weather in the affected districts before the harvest season. Coordinated international collaboration and steady financial supports are needed to mitigate the fearsome wheat blast in South Asia before it becomes a catastrophe.

Dose-Dependent Inhibition of Melanoma Differentiation-Associated Gene 5-Mediated Activation of Type I Interferon Responses by Methyltransferase of Hepatitis E Virus

  • Myoung, Jinjong;Min, Kang Sang
    • Journal of Microbiology and Biotechnology
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    • v.29 no.7
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    • pp.1137-1143
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    • 2019
  • Hepatitis E virus (HEV) accounts for 20 million infections in humans worldwide. In most cases, the infections are self-limiting while HEV genotype 1 infection cases may lead to lethal infections in pregnant women (~ 20% fatality). The lack of small animal models has hampered detailed analysis of virus-host interactions and HEV-induced pathology. Here, by employing a recently developed culture-adapted HEV, we demonstrated that methyltransferase, a non-structural protein, strongly inhibits melanoma differentiation-associated gene 5 (MDA5)-mediated activation of type I interferon responses. Compared to uninfected controls, HEV-infected cells display significantly lower levels of $IFN-{\beta}$ promoter activation when assessed by luciferase assay and RT-PCR. HEV genome-wide screening showed that HEV-encoded methyltransferase (MeT) strongly inhibits MDA5-mediated transcriptional activation of $IFN-{\beta}$ and $NF-{\kappa}B$ in a dose-responsive manner whether or not it is expressed in the presence/absence of a tag fused to it. Taken together, current studies clearly demonstrated that HEV MeT is a novel antagonist of MDA5-mediated induction of $IFN-{\beta}$ signaling.

Solution Conformations of the Substrates and Inhibitor of Hepatitis C Virus NS3 Protease

  • 이정훈;방근수;정진원;안인애;노성구;이원태
    • Bulletin of the Korean Chemical Society
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    • v.20 no.3
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    • pp.301-306
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    • 1999
  • Hepatitis C virus (HCV) has been known to be an enveloped virus with a positive strand RNA genome and the major agent of the vast majority of transfusion associated cases of hepatitis. For viral replication, HCV structural proteins are first processed by host cell signal peptidases and NS2/NS3 site of the nonstructural protein is cleaved by a zinc-dependent protease NS2 with N-terminal NS3. The four remaining junctions are cleaved by a separate NS3 protease. The solution conformations of NS4B/5A, NS5A/5B substrates and NS5A/5B inhibitor have been determined by two-dimensional nuclear magnetic resonance (NMR) spectroscopy. NMR data suggested that the both NS5A/5B substrate and inhibitor appeared to have a folded tum-like conformation not only between P1 and P6 position but also C-terminal region, whereas the NS4B/5A substrate exhibited mostly extended conformation. In addition, we have found that the conformation of the NS5A/5B inhibitor slightly differs from that of NS5A/5B substrate peptide, suggesting different binding mode for NS3 protease. These findings will be of importance for designing efficient inhibitor to suppress HCV processing.

Z-DNA-Containing Long Terminal Repeats of Human Endogenous Retrovirus Families Provide Alternative Promoters for Human Functional Genes

  • Lee, Du Hyeong;Bae, Woo Hyeon;Ha, Hongseok;Park, Eun Gyung;Lee, Yun Ju;Kim, Woo Ryung;Kim, Heui-Soo
    • Molecules and Cells
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    • v.45 no.8
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    • pp.522-530
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    • 2022
  • Transposable elements (TEs) account for approximately 45% of the human genome. TEs have proliferated randomly and integrated into functional genes during hominoid radiation. They appear as right-handed B-DNA double helices and slightly elongated left-handed Z-DNAs. Human endogenous retrovirus (HERV) families are widely distributed in human chromosomes at a ratio of 8%. They contain a 5'-long terminal repeat (LTR)-gag-pol-env-3'-LTR structure. LTRs contain the U3 enhancer and promoter region, transcribed R region, and U5 region. LTRs can influence host gene expression by acting as regulatory elements. In this review, we describe the alternative promoters derived from LTR elements that overlap Z-DNA by comparing Z-hunt and DeepZ data for human functional genes. We also present evidence showing the regulatory activity of LTR elements containing Z-DNA in GSDML. Taken together, the regulatory activity of LTR elements with Z-DNA allows us to understand gene function in relation to various human diseases.

Pathogenicity of infectious in vitro transcripts and comparison of RNA3 of Alfalfa mosaic virus Korean isolates

  • J.H. Ha;Park, J.K.;K.H. Ryu
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.146.2-147
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    • 2003
  • Two Korean isolates of Alfalfa mosaic virus (AHV-AZ, AMV-KR) were isolated from azuki bean and potato plants, respectively, and their pathologies were confirmed on some susceptible host plants including pepper, tobacco and red bean plants. Full length cDNAs to RNA1, RNA2 and RNA3 of the two Korean strains were amplified using the long-template reverse transcription (RT)-polymerase chain reaction (PCR) method. RT-PCR products covering entire regions for the three AMV genome RNAs were cloned. RNA transcripts were synthesized in vitro from each clones using T7 RNA polymerase and infectivity test was peformed in 9 reassortment sets of transcripts. All the combinations of reassorted transcripts were found to be infectious when inoculated onto Nicotiana benthamiana plants, and were not distinguishable to those of wild types. The full-length cDNA clones that were confirmed infectious were sequenced their nucleotide sequences. We will discuss sequence analysis of the two Korean isolates of AMV genomic RNA3 and compare reported foreign isolates of AMV.

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Lumpy skin disease as an emerging infectious disease

  • Hye Jin Eom;Eun-Seo Lee;Han Sang Yoo
    • Journal of Veterinary Science
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    • v.24 no.3
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    • pp.42.1-42.6
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    • 2023
  • Lumpy skin disease (LSD) is one of the most important emerging transboundary diseases. Recently, LSD has emerged in many countries in the northern hemisphere. The LSD virus has a huge genome and is highly resistant to environmental conditions. The virus is also host-specific and large ruminants, such as cattle and domestic water buffalo, are particularly susceptible. In addition, wild ruminants can serve as potential reservoirs for spreading the LSD virus. The emergence might be related to climate change in various regions because LSD is an arthropod-borne infectious disease. This disease causes enormous economic losses, such as leather damage, decreased milk production, abortion, and death in infected ruminants. The economic importance of LSD in the bovine industry has forced countries to develop and implement control strategies against the disease. With the recent global spread and the economic impact, LSD will be discussed intensively. In addition, effective preventive measures are suggested based on the presence or absence of LSD outbreaks.

Antibiotic resistance in Neisseria gonorrhoeae: broad-spectrum drug target identification using subtractive genomics

  • Umairah Natasya Mohd Omeershffudin;Suresh Kumar
    • Genomics & Informatics
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    • v.21 no.1
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    • pp.5.1-5.13
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    • 2023
  • Neisseria gonorrhoeae is a Gram-negative aerobic diplococcus bacterium that primarily causes sexually transmitted infections through direct human sexual contact. It is a major public health threat due to its impact on reproductive health, the widespread presence of antimicrobial resistance, and the lack of a vaccine. In this study, we used a bioinformatics approach and performed subtractive genomic methods to identify potential drug targets against the core proteome of N. gonorrhoeae (12 strains). In total, 12,300 protein sequences were retrieved, and paralogous proteins were removed using CD-HIT. The remaining sequences were analyzed for non-homology against the human proteome and gut microbiota, and screened for broad-spectrum analysis, druggability, and anti-target analysis. The proteins were also characterized for unique interactions between the host and pathogen through metabolic pathway analysis. Based on the subtractive genomic approach and subcellular localization, we identified one cytoplasmic protein, 2Fe-2S iron-sulfur cluster binding domain-containing protein (NGFG RS03485), as a potential drug target. This protein could be further exploited for drug development to create new medications and therapeutic agents for the treatment of N. gonorrhoeae infections.