Direct Relationship between Protein Expression and Progeny Yield of Herpes Simplex Virus 1 Unveils a Rate-limiting Step for Virus Production
Although viral protein expression and progeny virus production were independently shown to be highly heterogenous in individual cells, their direct relationship, analyzed by considering their heterogeneities, has not been investigated to date. This study established a system to fractionate cells inf...
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Main Authors | , , , , , , , , , , , , , , |
Format | Paper |
Language | Japanese |
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Cold Spring Harbor Laboratory
08.06.2023
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Edition | 1.2 |
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ISSN | 2692-8205 |
DOI | 10.1101/2023.06.07.544155 |
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Abstract | Although viral protein expression and progeny virus production were independently shown to be highly heterogenous in individual cells, their direct relationship, analyzed by considering their heterogeneities, has not been investigated to date. This study established a system to fractionate cells infected with a herpesvirus based on the levels of the global expression of viral late proteins, which are largely virion structural proteins, and to titrate virus yields in these fractions. This system demonstrated a direct relationship and indicated there was a threshold for the levels of viral late protein expression for progeny virus production and suggested that viral DNA cleavage/packaging was a rate-limiting step for progeny virus production. These findings, which were masked in previous studies performed at the entire population level, have uncovered a sophisticated viral strategy for efficient progeny virus production and shed new light on an effective target for the development of anti-viral drugs. |
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AbstractList | Although viral protein expression and progeny virus production were independently shown to be highly heterogenous in individual cells, their direct relationship, analyzed by considering their heterogeneities, has not been investigated to date. This study established a system to fractionate cells infected with a herpesvirus based on the levels of the global expression of viral late proteins, which are largely virion structural proteins, and to titrate virus yields in these fractions. This system demonstrated a direct relationship and indicated there was a threshold for the levels of viral late protein expression for progeny virus production and suggested that viral DNA cleavage/packaging was a rate-limiting step for progeny virus production. These findings, which were masked in previous studies performed at the entire population level, have uncovered a sophisticated viral strategy for efficient progeny virus production and shed new light on an effective target for the development of anti-viral drugs. |
Author | Kusano, Hideo Yoshimura, Raiki Adachi, Shungo Kawaguchi, Yasushi Maruzuru, Yuhei Kozaki, Yoshitaka Nobe, Moeka Nishiyama, Takara Koyanagi, Naoto Kato, Akihisa Iwami, Shingo Park, Hyeongki Maeda, Fumio Takeshima, Kosuke Natsume, Tohru |
Author_xml | – sequence: 1 givenname: Moeka surname: Nobe fullname: Nobe, Moeka organization: Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo – sequence: 2 givenname: Yuhei surname: Maruzuru fullname: Maruzuru, Yuhei organization: Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo – sequence: 3 givenname: Kosuke surname: Takeshima fullname: Takeshima, Kosuke organization: Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo – sequence: 4 givenname: Fumio surname: Maeda fullname: Maeda, Fumio organization: Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST) – sequence: 5 givenname: Hideo surname: Kusano fullname: Kusano, Hideo organization: Japan – sequence: 6 givenname: Raiki surname: Yoshimura fullname: Yoshimura, Raiki organization: Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University – sequence: 7 givenname: Takara surname: Nishiyama fullname: Nishiyama, Takara organization: Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University – sequence: 8 givenname: Hyeongki surname: Park fullname: Park, Hyeongki organization: Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University – sequence: 9 givenname: Yoshitaka surname: Kozaki fullname: Kozaki, Yoshitaka organization: Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University – sequence: 10 givenname: Shingo surname: Iwami fullname: Iwami, Shingo organization: Interdisciplinary Biology Laboratory (iBLab), Division of Biological Science, Graduate School of Science, Nagoya University – sequence: 11 givenname: Naoto surname: Koyanagi fullname: Koyanagi, Naoto organization: Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo – sequence: 12 givenname: Akihisa surname: Kato fullname: Kato, Akihisa organization: Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo – sequence: 13 givenname: Tohru surname: Natsume fullname: Natsume, Tohru organization: Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST) – sequence: 14 givenname: Shungo surname: Adachi fullname: Adachi, Shungo organization: Japan – sequence: 15 givenname: Yasushi surname: Kawaguchi fullname: Kawaguchi, Yasushi email: ykawagu@ims.u-tokyo.ac.jp organization: Infection and Advanced Research Center |
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Title | Direct Relationship between Protein Expression and Progeny Yield of Herpes Simplex Virus 1 Unveils a Rate-limiting Step for Virus Production |
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