scholarly journals Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for coronavirus replication

2021 ◽  
Vol 17 (12) ◽  
pp. e1010113
Author(s):  
Limeng Sun ◽  
Changzhi Zhao ◽  
Zhen Fu ◽  
Yanan Fu ◽  
Zhelin Su ◽  
...  
Keyword(s):  
Early Stage ◽  
Transmembrane Protein ◽  
Animal Health ◽  
Membrane Vesicles ◽  
Host Factor ◽  
Transmissible Gastroenteritis Virus ◽  
Infection Model ◽  
Mouse Infection Model ◽  
Transmissible Gastroenteritis ◽  
Genome Scale

Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. We found that TMEM41B is critical for the internalization and early-stage replication of TGEV. Notably, our results also showed that cells lacking TMEM41B are unable to form the double-membrane vesicles necessary for TGEV replication, indicating that TMEM41B contributes to the formation of CoV replication organelles. Lastly, our data from a mouse infection model showed that the KO of this factor can strongly inhibit viral infection and delay the progression of a CoV disease. Our study revealed that targeting TMEM41B is a highly promising approach for the development of broad-spectrum anti-viral therapeutics.

THE OUTBREAK OF PORCINE EPIDEMIC DIARRHEA IN TAIWAN

2014 ◽  
Vol 40 (03) ◽  
pp. 115-121 ◽  
Author(s):  
Ming-Chung Deng ◽  
Chia-Yi Chang ◽  
Tien-Shine Huang ◽  
Shu-Ting Kuo ◽  
Hsiang-Jung Tsai ◽  
...  
Keyword(s):  
Animal Health ◽  
Vero Cells ◽  
Transmissible Gastroenteritis Virus ◽  
Rt Pcr ◽  
Sequence Comparisons ◽  
Diarrhea Virus ◽  
Severe Diarrhea ◽  
Porcine Epidemic Diarrhea ◽  
Transmissible Gastroenteritis ◽  
Group 2

Between January 20 and April 30 of 2014, a total of 103 diarrhea cases from 47 herds in 13 counties were submitted to the Animal Health Research Institute. In 20 of the 25 herds with detail history, severe diarrhea and vomiting occurred in pigs of all ages, with mortality approaching 100% in suckling pigs. The differential etiologies, including transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine group A rotavirus (GARV), were tested by reverse transcription polymerase chain reaction (RT-PCR). The RT-PCR of PEDV was positive in 79 cases of 34 herds. Attempts to isolate PEDV in Vero cells revealed that only 7 specimens from 7 herds showed the cytopathic effects (CPEs) of fusion and syncytia. These CPEs were indeed caused by PEDV, as confirmed by RT-PCR, sequencing, and electron microscopy. Sequence comparisons of diarrhea samples and isolated PEDV were assayed by MEGA 5.2 software. The newly isolated PEDV/Taiwan/2014 strains were clustered in group 2 as novel PEDV, together with strains PEDV/USA/2013, PEDV/China/2011–2013, PEDV/Thailand/2007–2008, and PEDV/Korea/2008–2009, whereas the classical CV777 strain was placed in a separate group 1. These results indicated that a novel PEDV was the cause of the recent new outbreak of diarrhea in Taiwan.

scholarly journals Antiviral and virucidal effects of curcumin on transmissible gastroenteritis virus in vitro

2020 ◽  
Vol 101 (10) ◽  
pp. 1079-1084 ◽  
Author(s):  
Yaoming Li ◽  
Jing Wang ◽  
Yinchuan Liu ◽  
Xiang Luo ◽  
Weiqiang Lei ◽  
...  
Keyword(s):  
Animal Health ◽  
Effective Control ◽  
Transmissible Gastroenteritis Virus ◽  
Dependent Manner ◽  
Gastroenteritis Virus ◽  
Candidate Drug ◽  
Transmissible Gastroenteritis ◽  
First Time ◽  
Dose Dependent

Emerging coronaviruses represent serious threats to human and animal health worldwide, and no approved therapeutics are currently available. Here, we used Transmissible gastroenteritis virus (TGEV) as the alpha-coronavirus model, and investigated the antiviral properties of curcumin against TGEV. Our results demonstrated that curcumin strongly inhibited TGEV proliferation and viral protein expression in a dose-dependent manner. We also observed that curcumin exhibited direct virucidal abilities in a dose-, temperature- and time-dependent manner. Furthermore, time-of-addition assays showed that curcumin mainly acted in the early phase of TGEV replication. Notably, in an adsorption assay, curcumin at 40 µM resulted in a reduction in viral titres of 3.55 log TCID50 ml–1, indicating that curcumin possesses excellent inhibitory effects on the adsorption of TGEV. Collectively, we demonstrate for the first time that curcumin has virucidal activity and virtual inhibition against TGEV, suggesting that curcumin might be a candidate drug for effective control of TGEV infection.

scholarly journals An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lucie Jelínková ◽  
Hugo Jhun ◽  
Allison Eaton ◽  
Nikolai Petrovsky ◽  
Fidel Zavala ◽  
...  
Keyword(s):  
Mouse Model ◽  
Malaria Vaccine ◽  
High Titer ◽  
Circumsporozoite Protein ◽  
Infection Model ◽  
Vaccine Platform ◽  
Junctional Region ◽  
Mouse Infection Model ◽  
Virus Like Particle ◽  
Major Surface

AbstractA malaria vaccine that elicits long-lasting protection and is suitable for use in endemic areas remains urgently needed. Here, we assessed the immunogenicity and prophylactic efficacy of a vaccine targeting a recently described epitope on the major surface antigen on Plasmodium falciparum sporozoites, circumsporozoite protein (CSP). Using a virus-like particle (VLP)-based vaccine platform technology, we developed a vaccine that targets the junctional region between the N-terminal and central repeat regions of CSP. This region is recognized by monoclonal antibodies, including mAb CIS43, that have been shown to potently prevent liver invasion in animal models. We show that CIS43 VLPs elicit high-titer and long-lived anti-CSP antibody responses in mice and is immunogenic in non-human primates. In mice, vaccine immunogenicity was enhanced by using mixed adjuvant formulations. Immunization with CIS43 VLPs conferred partial protection from malaria infection in a mouse model, and passive transfer of serum from immunized macaques also inhibited parasite liver invasion in the mouse infection model. Our findings demonstrate that a Qβ VLP-based vaccine targeting the CIS43 epitope combined with various adjuvants is highly immunogenic in mice and macaques, elicits long-lasting anti-CSP antibodies, and inhibits parasite infection in a mouse model. Thus, the CIS43 VLP vaccine is a promising pre-erythrocytic malaria vaccine candidate.

scholarly journals Data standardization implementation and applications within and among diagnostic laboratories: integrating and monitoring enteric coronaviruses

2021 ◽  
pp. 104063872110021
Author(s):  
Giovani Trevisan ◽  
Leticia C. M. Linhares ◽  
Kent J. Schwartz ◽  
Eric R. Burrough ◽  
Edison de S. Magalhães ◽  
...  
Keyword(s):  
Seasonal Pattern ◽  
Laboratory Data ◽  
Information Management System ◽  
Transmissible Gastroenteritis Virus ◽  
Test Results ◽  
Diarrhea Virus ◽  
Oral Fluids ◽  
Transmissible Gastroenteritis ◽  
Technology Processes ◽  
Laboratory Information Management

Every day, thousands of samples from diverse populations of animals are submitted to veterinary diagnostic laboratories (VDLs) for testing. Each VDL has its own laboratory information management system (LIMS), with processes and procedures to capture submission information, perform laboratory tests, define the boundaries of test results (i.e., positive or negative), and report results, in addition to internal business and accounting applications. Enormous quantities of data are accumulated and stored within VDL LIMSs. There is a need for platforms that allow VDLs to exchange and share portions of laboratory data using standardized, reliable, and sustainable information technology processes. Here we report concepts and applications for standardization and aggregation of data from swine submissions to multiple VDLs to detect and monitor porcine enteric coronaviruses by RT-PCR. Oral fluids, feces, and fecal swabs were the specimens submitted most frequently for enteric coronavirus testing. Statistical algorithms were used successfully to scan and monitor the overall and state-specific percentage of positive submissions. Major findings revealed a consistently recurrent seasonal pattern, with the highest percentage of positive submissions detected during December–February for porcine epidemic diarrhea virus, porcine deltacoronavirus, and transmissible gastroenteritis virus (TGEV). After 2014, very few submissions tested positive for TGEV. Monitoring VDL data proactively has the potential to signal and alert stakeholders early of significant changes from expected detection. We demonstrate the importance of, and applications for, data organized and aggregated by using LOINC and SNOMED CTs, as well as the use of customized messaging to allow inter-VDL exchange of information.

scholarly journals Reverse Genetic Analysis of the Transcription Regulatory Sequence of the Coronavirus Transmissible Gastroenteritis Virus

2004 ◽  
Vol 78 (11) ◽  
pp. 6061-6066 ◽  
Author(s):  
Kristopher M. Curtis ◽  
Boyd Yount ◽  
Amy C. Sims ◽  
Ralph S. Baric
Keyword(s):  
Genetic Analysis ◽  
Full Length ◽  
Transmissible Gastroenteritis Virus ◽  
Regulatory Sequence ◽  
Reverse Genetic ◽  
Conserved Sequence ◽  
Gastroenteritis Virus ◽  
Flanking Sequences ◽  
Transmissible Gastroenteritis ◽  
Discontinuous Transcription

ABSTRACT Coronavirus discontinuous transcription uses a highly conserved sequence (CS) in the joining of leader and body RNAs. Using a full-length infectious construct of transmissable gastroenteritis virus, the present study demonstrates that subgenomic transcription is heavily influenced by upstream flanking sequences and supports a mechanism of transcription attenuation that is regulated in part by a larger domain composed of primarily upstream flanking sequences which select appropriately positioned CS elements for synthesis of subgenomic RNAs.

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