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2. Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication

Author

Kindler, Eveline, Gil-Cruz, Cristina, Spanier, Julia, Li, Yize, Wilhelm, Jochen, Rabouw, Huib H, Züst, Roland, Hwang, Mihyun, V'kovski, Philip, Stalder, Hanspeter, Marti, Sabrina, Habjan, Matthias, Cervantes-Barragan, Luisa, Elliot, Ruth, Karl, Nadja, Gaughan, Christina, van Kuppeveld, Frank J M, Silverman, Robert H, Keller, Markus, Ludewig, Burkhard, Bergmann, Cornelia C, Ziebuhr, John, Weiss, Susan R, Kalinke, Ulrich, Thiel, Volker, Kindler, Eveline, Gil-Cruz, Cristina, Spanier, Julia, Li, Yize, Wilhelm, Jochen, Rabouw, Huib H, Züst, Roland, Hwang, Mihyun, V'kovski, Philip, Stalder, Hanspeter, Marti, Sabrina, Habjan, Matthias, Cervantes-Barragan, Luisa, Elliot, Ruth, Karl, Nadja, Gaughan, Christina, van Kuppeveld, Frank J M, Silverman, Robert H, Keller, Markus, Ludewig, Burkhard, Bergmann, Cornelia C, Ziebuhr, John, Weiss, Susan R, Kalinke, Ulrich, and Thiel, Volker

Abstract

Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis-within the replicase complex-suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.

Published
2017

3. Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication

Author

dI&I I&I-1, LS Virologie, Kindler, Eveline, Gil-Cruz, Cristina, Spanier, Julia, Li, Yize, Wilhelm, Jochen, Rabouw, Huib H, Züst, Roland, Hwang, Mihyun, V'kovski, Philip, Stalder, Hanspeter, Marti, Sabrina, Habjan, Matthias, Cervantes-Barragan, Luisa, Elliot, Ruth, Karl, Nadja, Gaughan, Christina, van Kuppeveld, Frank J M, Silverman, Robert H, Keller, Markus, Ludewig, Burkhard, Bergmann, Cornelia C, Ziebuhr, John, Weiss, Susan R, Kalinke, Ulrich, Thiel, Volker, dI&I I&I-1, LS Virologie, Kindler, Eveline, Gil-Cruz, Cristina, Spanier, Julia, Li, Yize, Wilhelm, Jochen, Rabouw, Huib H, Züst, Roland, Hwang, Mihyun, V'kovski, Philip, Stalder, Hanspeter, Marti, Sabrina, Habjan, Matthias, Cervantes-Barragan, Luisa, Elliot, Ruth, Karl, Nadja, Gaughan, Christina, van Kuppeveld, Frank J M, Silverman, Robert H, Keller, Markus, Ludewig, Burkhard, Bergmann, Cornelia C, Ziebuhr, John, Weiss, Susan R, Kalinke, Ulrich, and Thiel, Volker

Published
2017

4. Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication

Author

Kindler, Eveline, primary, Gil-Cruz, Cristina, additional, Spanier, Julia, additional, Li, Yize, additional, Wilhelm, Jochen, additional, Rabouw, Huib H., additional, Züst, Roland, additional, Hwang, Mihyun, additional, V’kovski, Philip, additional, Stalder, Hanspeter, additional, Marti, Sabrina, additional, Habjan, Matthias, additional, Cervantes-Barragan, Luisa, additional, Elliot, Ruth, additional, Karl, Nadja, additional, Gaughan, Christina, additional, van Kuppeveld, Frank J. M., additional, Silverman, Robert H., additional, Keller, Markus, additional, Ludewig, Burkhard, additional, Bergmann, Cornelia C., additional, Ziebuhr, John, additional, Weiss, Susan R., additional, Kalinke, Ulrich, additional, and Thiel, Volker, additional

Published
2017
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5. The information highway: rules of the road

Author

Elliot, Ruth Layman

Subjects
Information technology -- Study and teaching, Nurses -- Education, Internet -- Usage
Abstract

Nurses should educate themselves on the impacts and uses of information technology and the Internet. Knowledge of the history of the Internet, computer technology, and uses of technology in health care environments can help nurses work confidently in the information age. Computer software accessibility and exploring the internet are excellent starting points in Internet travel.

Published
1996

7. Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication

Author

Kindler, Eveline Patricia, Gil-Cruz, Cristina, Spanier, Julia, Li, Yize, Wilhelm, Jochen, Rabouw, Huib H, Züst, Roland, Hwang, Mihyun, V'Kovski, Philip, Stalder, Hanspeter, Marti, Sabrina, Habjan, Matthias, Cervantes-Barragan, Luisa, Elliot, Ruth, Karl, Nadja, Gaughan, Christina, Van Kuppeveld, Frank J M, Silverman, Robert H, Keller, Markus, Ludewig, Burkhard, Bergmann, Cornelia C, Ziebuhr, John, Weiss, Susan R, Kalinke, Ulrich, and Thiel, Volker Earl

Subjects
630 Agriculture, viruses, 570 Life sciences, biology, 3. Good health
Abstract

Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis-within the replicase complex-suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses.

9. Repair shop trains jobless Londoners

Author

Elliot, Ruth

Subjects
Home appliances -- Maintenance and repair, Furniture finishing -- Study and teaching, Unemployed workers -- Training
Published
1980

10. Letters to the Editor.

Author

Tumlinson, Marie, Nugrad, Mildred, Barclay, James W., Marvin, Frances A., Rothert, L. Wesley, Cohen, Edna, Gabriel, Mary, Elliot, Ruth C., Smith, Nellie K., Broe, Francis, Clark, Betty, Kennedy, William D., and Brougton, D. F.

Subjects
LETTERS to the editor, JAPANESE art, WATERCOLOR painting, ARTISTS
Abstract

Several letters to the editor are presented in response to articles in previous issues including one by Charles E. Luffman about Japanese art in the May 1959 issue, another by Arnold Burchess about watercolors in the summer 1959 issue and an article by Henry Pitz about the work of Edward Redfield in the April 1959 issue.

Published
1959

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