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BHK-21 clone 13

RRID:CVCL_1915

Organism

Mesocricetus auratus

Comments

Doubling time: ~32-50 hours (DSMZ). DT Created: 04-04-12; Last updated: 05-07-19; Version: 20

Proper Citation

KCB Cat# KCB 92005YJ, RRID:CVCL_1915

Category

Spontaneously immortalized cell line DT Created: 04-04-12; Last updated: 05-07-19; Version: 20

Sex

DT Created: 04-04-12; Last updated: 05-07-19; Version: 20

Synonyms

BHK 21 clone 13, BHK21 clone 13, BHK-21 (clone 13), BHK 21 (clone 13), BHK21 (clone-13), BHK-21 (C-13), BHK-21 [C-13], BHK-21(C-13), BHK-21(C13), BHK-21 C-13, BHK-21-C13, BHK-21/C13, BHK 21 CL13, BHK 21 C13, BHK21-C13, BHK-21 C 13, BHK 21/13, BHK21/C13, BHK21/13, BHK21 C13, BHK21C13, C13, BHK-21-ATCC DT Created: 04-04-12, Last updated: 05-07-19, Version: 20

Vendor

KCB

Cat Num

KCB 92005YJ

Cross References

CLO; CLO_0001957 CLO; CLO_0001958 CLO; CLO_0001959 CLO; CLO_0001965 CLO; CLO_0001966 CLO; CLO_0001967 CLO; CLO_0051403 CLDB; cl439 CLDB; cl444 CLDB; cl445 CLDB; cl446 CLDB; cl447 CLDB; cl448 ATCC; CCL-10 BCRC; 60041 BCRJ; 0050 CCLV; CCLV-RIE 0179 CCLV; CCLV-RIE 0194 CCRID; 3111C0001CCC000097 CCRID; 3111C0002000000033 CCRID; 3131C0001000100001 CCRID; 3142C0001000000010 CCRID; 3153C0001000000036 CCTCC; GDC0010 ChEMBL-Cells; CHEMBL3308360 ChEMBL-Targets; CHEMBL614527 CLS; 603126/p632_BHK-21 DSMZ; ACC-61 ECACC; 85011433 ECACC; 93120815 FCS-free; 46-8-47-1-8-9 FCS-free; 46-8-338-1-16-3 IZSLER; BS CL 8 JCRB; JCRB9020 KCB; KCB 90020YJ KCB; KCB 92005YJ KCLB; 10010 Lonza; 762 NCBI_Iran; C107 RCB; RCB1423 TKG; TKG 0308 TOKU-E; 667 Wikidata; Q54796388 DT Created: 04-04-12; Last updated: 05-07-19; Version: 20

Hierarchy

DT Created: 04-04-12; Last updated: 05-07-19; Version: 20

Immunomimetic Designer Cells Protect Mice from MRSA Infection.

  • Liu Y
  • Cell
  • 2018 Jun 12

Literature context:


Abstract:

Many community- and hospital-acquired bacterial infections are caused by antibiotic-resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) predisposes humans to invasive infections that are difficult to eradicate. We designed a closed-loop gene network programming mammalian cells to autonomously detect and eliminate bacterial infections. The genetic circuit contains human Toll-like receptors as the bacterial sensor and a synthetic promoter driving reversible and adjustable expression of lysostaphin, a bacteriolytic enzyme highly lethal to S. aureus. Immunomimetic designer cells harboring this genetic circuit exhibited fast and robust sense-and-destroy kinetics against live staphylococci. When tested in a foreign-body infection model in mice, microencapsulated cell implants prevented planktonic MRSA infection and reduced MRSA biofilm formation by 91%. Notably, this system achieved a 100% cure rate of acute MRSA infections, whereas conventional vancomycin treatment failed. These results suggest that immunomimetic designer cells could offer a therapeutic approach for early detection, prevention, and cure of pathogenic infections in the post-antibiotic era.

Funding information:
  • Biotechnology and Biological Sciences Research Council - BB/J015652/1(United Kingdom)

Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses.

  • Webster B
  • Elife
  • 2018 Jun 19

Literature context:


Abstract:

Type I interferon (IFN-I) responses are critical for the control of RNA virus infections, however, many viruses, including Dengue (DENV) and Chikungunya (CHIKV) virus, do not directly activate plasmacytoid dendritic cells (pDCs), robust IFN-I producing cells. Herein, we demonstrated that DENV and CHIKV infected cells are sensed by pDCs, indirectly, resulting in selective IRF7 activation and IFN-I production, in the absence of other inflammatory cytokine responses. To elucidate pDC immunomodulatory functions, we developed a mouse model in which IRF7 signaling is restricted to pDC. Despite undetectable levels of IFN-I protein, pDC-restricted IRF7 signaling controlled both viruses and was sufficient to protect mice from lethal CHIKV infection. Early pDC IRF7-signaling resulted in amplification of downstream antiviral responses, including an accelerated natural killer (NK) cell-mediated type II IFN response. These studies revealed the dominant, yet indirect role of pDC IRF7-signaling in directing both type I and II IFN responses during arbovirus infections.

Funding information:
  • Agence Nationale de la Recherche - ANR-11-LABX-0048()
  • Agence Nationale de la Recherche - ANR-14-CE14-0015-02 CHIKV-Viro-Immuno()
  • Agence Nationale de la Recherche - ANR-JCJC-EXAMIN()
  • Agence Nationale de Recherches sur le Sida et les Hepatites Virales - ANRS-AO 2016-01()
  • Wellcome Trust - WT066784/Z/02/Z(United Kingdom)

Combined Human Genome-wide RNAi and Metabolite Analyses Identify IMPDH as a Host-Directed Target against Chlamydia Infection.

  • Rother M
  • Cell Host Microbe
  • 2018 May 9

Literature context:


Abstract:

Chlamydia trachomatis (Ctr) accounts for >130 million human infections annually. Since chronic Ctr infections are extremely difficult to treat, there is an urgent need for more effective therapeutics. As an obligate intracellular bacterium, Ctr strictly depends on the functional contribution of the host cell. Here, we combined a human genome-wide RNA interference screen with metabolic profiling to obtain detailed understanding of changes in the infected cell and identify druggable pathways essential for Ctr growth. We demonstrate that Ctr shifts the host metabolism toward aerobic glycolysis, consistent with increased biomass requirement. We identify key regulator complexes of glucose and nucleotide metabolism that govern Ctr infection processes. Pharmacological targeting of inosine-5'-monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in guanine nucleotide biosynthesis, efficiently inhibits Ctr growth both in vitro and in vivo. These results highlight the potency of genome-scale functional screening for the discovery of drug targets against bacterial infections.

Funding information:
  • Wellcome Trust - 094879(United Kingdom)

The Efficacy of the Interferon Alpha/Beta Response versus Arboviruses Is Temperature Dependent.

  • Lane WC
  • MBio
  • 2018 Apr 24

Literature context:


Abstract:

Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency. Here, we demonstrate that the IFN-α/β response against multiple arthropod-vectored viruses, which replicate over a wide temperature range, is extremely sensitive to fluctuations in temperature, exhibiting reduced antiviral efficacy at subnormal cellular temperatures and increased efficacy at supranormal temperatures. The effect involves both IFN-α/β and ISG upregulation pathways with a major aspect of altered potency reflecting highly temperature-dependent transcription of IFN response genes that leads to altered IFN-α/β and ISG protein levels. Discordantly, signaling steps prior to transcription that were examined showed the opposite effect from gene transcription, with potentiation at low temperature and inhibition at high temperature. Finally, we demonstrate that by lowering the temperature of mice, chikungunya arbovirus replication and disease are exacerbated in an IFN-α/β-dependent manner. This finding raises the potential for use of hyperthermia as a therapeutic modality for viral infections and in other contexts such as antitumor therapy. The increased IFN-α/β efficacy at high temperatures may also reflect an innate immune-relevant aspect of the febrile response.IMPORTANCE The interferon alpha/beta (IFN-α/β) response is a first-line innate defense against arthropod-borne viruses (arboviruses). Arboviruses, such as chikungunya virus (CHIKV), can infect cells and replicate across a wide temperature range due to their replication in both mammalian/avian and arthropod hosts. Accordingly, these viruses can cause human disease in tissues regularly exposed to temperatures below the normal mammalian core temperature, 37°C. We questioned whether temperature variation could affect the efficacy of IFN-α/β responses against these viruses and help to explain some aspects of human disease manifestations. We observed that IFN-α/β efficacy was dramatically lower at subnormal temperatures and modestly enhanced at febrile temperatures, with the effects involving altered IFN-α/β response gene transcription but not IFN-α/β pathway signaling. These results provide insight into the functioning of the IFN-α/β response in vivo and suggest that temperature elevation may represent an immune-enhancing therapeutic modality for a wide variety of IFN-α/β-sensitive infections and pathologies.

Funding information:
  • NIAID NIH HHS - R01 AI095436()
  • NIAID NIH HHS - T32 AI049820()
  • NIAID NIH HHS - T32 AI060525()
  • NIAMS NIH HHS - R00AR056899-03(United States)
  • NIH HHS - S10 OD019973()

Dichotomous Expression of TNF Superfamily Ligands on Antigen-Presenting Cells Controls Post-priming Anti-viral CD4+ T Cell Immunity.

  • Chang YH
  • Immunity
  • 2017 Nov 21

Literature context:


Abstract:

T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4+ T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs). Mice with hypofunctional GITRL in Lyz2+ cells had decreased LCMV-specific CD4+ T cell accumulation and increased viral load. GITR signals in CD4+ T cells occurred after priming to upregulate OX40, CD25, and chemokine receptor CX3CR1. Thus IFN-I (signal 3) induced a post-priming checkpoint (signal 4) for CD4+ T cell accumulation, revealing a division of labor between cDCs and monocyte-derived APCs in regulating T cell expansion.

Funding information:
  • NIA NIH HHS - P01 AG017617(United States)

Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments.

  • Barski M
  • Elife
  • 2017 Sep 15

Literature context:


Abstract:

Rift Valley fever phlebovirus (RVFV) is a clinically and economically important pathogen increasingly likely to cause widespread epidemics. RVFV virulence depends on the interferon antagonist non-structural protein (NSs), which remains poorly characterized. We identified a stable core domain of RVFV NSs (residues 83-248), and solved its crystal structure, a novel all-helical fold organized into highly ordered fibrils. A hallmark of RVFV pathology is NSs filament formation in infected cell nuclei. Recombinant virus encoding the NSs core domain induced intranuclear filaments, suggesting it contains all essential determinants for nuclear translocation and filament formation. Mutations of key crystal fibril interface residues in viruses encoding full-length NSs completely abrogated intranuclear filament formation in infected cells. We propose the fibrillar arrangement of the NSs core domain in crystals reveals the molecular basis of assembly of this key virulence factor in cell nuclei. Our findings have important implications for fundamental understanding of RVFV virulence.

Funding information:
  • NIMH NIH HHS - R37 MH063394(United States)

Interferon-γ-Driven iNOS: A Molecular Pathway to Terminal Shock in Arenavirus Hemorrhagic Fever.

  • Remy MM
  • Cell Host Microbe
  • 2017 Sep 13

Literature context:


Abstract:

Arenaviruses such as Lassa virus (LASV) cause hemorrhagic fever. Terminal shock is associated with a systemic cytokine storm, but the mechanisms are ill defined. Here we used HLA-A2-expressing mice infected with a monkey-pathogenic strain of lymphocytic choriomeningitis virus (LCMV-WE), a close relative of LASV, to investigate the pathophysiology of arenavirus hemorrhagic fever (AHF). AHF manifested as pleural effusions, edematous skin swelling, and serum albumin loss, culminating in hypovolemic shock. A characteristic cytokine storm included numerous pro-inflammatory cytokines and nitric oxide (NO) metabolites. Edema formation and terminal shock were abrogated in mice lacking inducible nitric oxide synthase (iNOS), although the cytokine storm persisted. iNOS was upregulated in the liver in a T cell- and interferon-γ (IFN-γ)-dependent fashion. Accordingly, blockade of IFN-γ or depletion of T cells repressed hepatic iNOS and prevented disease despite unchecked high-level viremia. We identify the IFN-γ-iNOS axis as an essential and potentially druggable molecular pathway to AHF-induced shock.

CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry.

  • Fros JJ
  • Elife
  • 2017 Sep 29

Literature context:


Abstract:

Most vertebrate and plant RNA and small DNA viruses suppress genomic CpG and UpA dinucleotide frequencies, apparently mimicking host mRNA composition. Artificially increasing CpG/UpA dinucleotides attenuates viruses through an entirely unknown mechanism. Using the echovirus 7 (E7) model in several cell types, we show that the restriction in E7 replication in mutants with increased CpG/UpA dinucleotides occurred immediately after viral entry, with incoming virions failing to form replication complexes. Sequences of CpG/UpA-high virus stocks showed no evidence of increased mutational errors that would render them replication defective, these viral RNAs were not differentially sequestered in cytoplasmic stress granules nor did they induce a systemic antiviral state. Importantly, restriction was not mediated through effects on translation efficiency since replicons with high CpG/UpA sequences inserted into a non-coding region were similarly replication defective. Host-cells thus possess intrinsic defence pathways that prevent replication of viruses with increased CpG/UpA frequencies independently of codon usage.

Lck/Hck/Fgr-Mediated Tyrosine Phosphorylation Negatively Regulates TBK1 to Restrain Innate Antiviral Responses.

  • Liu S
  • Cell Host Microbe
  • 2017 Jun 14

Literature context:


Abstract:

Cytosolic nucleic acid sensing elicits interferon production for primary antiviral defense through cascades controlled by protein ubiquitination and Ser/Thr phosphorylation. Here we show that TBK1, a core kinase of antiviral pathways, is inhibited by tyrosine phosphorylation. The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation. Accordingly, antiviral sensing and resistance were substantially enhanced in Lck/Hck/Fgr triple knockout cells and ectopic expression of Lck/Hck/Fgr dampened the antiviral defense in cells and zebrafish. Small-molecule inhibitors of SFKs, which are conventional anti-tumor therapeutics, enhanced antiviral responses and protected zebrafish and mice from viral attack. Viral infection induced the expression of Lck/Hck/Fgr through TBK1-mediated mobilization of IRF3, thus constituting a negative feedback loop. These findings unveil the negative regulation of TBK1 via tyrosine phosphorylation and the functional integration of SFKs into innate antiviral immunity.

Circulating Immune Cells Mediate a Systemic RNAi-Based Adaptive Antiviral Response in Drosophila.

  • Tassetto M
  • Cell
  • 2017 Apr 6

Literature context:


Abstract:

Effective antiviral protection in multicellular organisms relies on both cell-autonomous and systemic immunity. Systemic immunity mediates the spread of antiviral signals from infection sites to distant uninfected tissues. In arthropods, RNA interference (RNAi) is responsible for antiviral defense. Here, we show that flies have a sophisticated systemic RNAi-based immunity mediated by macrophage-like haemocytes. Haemocytes take up dsRNA from infected cells and, through endogenous transposon reverse transcriptases, produce virus-derived complementary DNAs (vDNA). These vDNAs template de novo synthesis of secondary viral siRNAs (vsRNA), which are secreted in exosome-like vesicles. Strikingly, exosomes containing vsRNAs, purified from haemolymph of infected flies, confer passive protection against virus challenge in naive animals. Thus, similar to vertebrates, insects use immune cells to generate immunological memory in the form of stable vDNAs that generate systemic immunity, which is mediated by the vsRNA-containing exosomes.

Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice.

  • Ma W
  • Cell
  • 2016 Dec 1

Literature context:


Abstract:

Zika virus (ZIKV) persists in the semen of male patients, a first for flavivirus infection. Here, we demonstrate that ZIKV can induce inflammation in the testis and epididymidis, but not in the prostate or seminal vesicle, and can lead to damaged testes after 60 days post-infection in mice. ZIKV induces innate immune responses in Leydig, Sertoli, and epididymal epithelial cells, resulting in the production of pro-inflammatory cytokines/chemokines. However, ZIKV does not induce a rapid and abundant cytokine production in peritubular cell and spermatogonia, suggesting that these cells are vulnerable for ZIKV infection and could be the potential repositories for ZIKV. Our study demonstrates a correlation between ZIKV and testis infection/damage and suggests that ZIKV infection, under certain circumstances, can eventually lead to male infertility.

Funding information:
  • NHLBI NIH HHS - T32 HL007088(United States)