Direct relationship between protein expression and progeny yield of herpes simplex virus 1

Earlier single-cell studies of virus-infected cells have revealed high heterogeneity in the state of viral gene expression and progeny virus yield. Notably, these two aspects have been shown independently, and therefore, the direct relationship between progeny virus production and viral gene express...

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Published inmBio Vol. 16; no. 6; p. e0028025
Main Authors Nobe, Moeka, Maruzuru, Yuhei, Takeshima, Kosuke, Maeda, Fumio, Kusano, Hideo, Yoshimura, Raiki, Nishiyama, Takara, Park, Hyeongki, Kozaki, Yoshitaka, Iwami, Shingo, Koyanagi, Naoto, Kato, Akihisa, Natsume, Tohru, Adachi, Shungo, Kawaguchi, Yasushi
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 11.06.2025
Subjects
Animals
Cell Line
Chlorocebus aethiops
Gene Expression Regulation, Viral
Genes, Reporter
herpes simplex virus
Herpesvirus 1, Human - genetics
Herpesvirus 1, Human - physiology
heterogeneity of infection
Humans
Nucleocapsid - metabolism
rate-limiting step for virus production
Research Article
Vero Cells
Viral Proteins - biosynthesis
Viral Proteins - genetics
Viral Proteins - metabolism
Virology
Virus Replication
herpes simplex virus
rate-limiting step for virus production
heterogeneity of infection
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Abstract Earlier single-cell studies of virus-infected cells have revealed high heterogeneity in the state of viral gene expression and progeny virus yield. Notably, these two aspects have been shown independently, and therefore, the direct relationship between progeny virus production and viral gene expression has been unclear. This study, for the first time, demonstrated the direct and quantitative relationship between viral protein expression and progeny virus production by taking into account their heterogeneities and revealed a threshold for the levels of herpes simplex virus 1 protein expression for progeny virus production, thereby suggesting the existence of a rate-limiting step in progeny virus production.
AbstractList Although viral protein expression and progeny virus production were independently shown to be highly heterogeneous in individual cells, their direct relationship, analyzed by considering their heterogeneities, has not been investigated to date. To elucidate the direct relationship between viral protein expression and progeny virus production, we constructed a reporter herpes simplex virus 1 (HSV-1) by tagging Venus to the late protein Us11. We then separated the HSV-1-infected cell population into multiple subpopulations according to the fluorescence intensity of Venus-which reflected the expression of L proteins, largely constituting virion structural proteins-and titrated virus yields and performed electron microscopic analysis in each subpopulation. Our results revealed that infectious progeny virus production, as well as nucleocapsid maturation, was triggered only when L protein expression exceeded a specific threshold. This suggested the existence of a rate-limiting step in progeny virus production, with nucleocapsid maturation potentially being one such step.IMPORTANCEEarlier single-cell studies of virus-infected cells have revealed high heterogeneity in the state of viral gene expression and progeny virus yield. Notably, these two aspects have been shown independently, and therefore, the direct relationship between progeny virus production and viral gene expression has been unclear. This study, for the first time, demonstrated the direct and quantitative relationship between viral protein expression and progeny virus production by taking into account their heterogeneities and revealed a threshold for the levels of herpes simplex virus 1 protein expression for progeny virus production, thereby suggesting the existence of a rate-limiting step in progeny virus production.
Earlier single-cell studies of virus-infected cells have revealed high heterogeneity in the state of viral gene expression and progeny virus yield. Notably, these two aspects have been shown independently, and therefore, the direct relationship between progeny virus production and viral gene expression has been unclear. This study, for the first time, demonstrated the direct and quantitative relationship between viral protein expression and progeny virus production by taking into account their heterogeneities and revealed a threshold for the levels of herpes simplex virus 1 protein expression for progeny virus production, thereby suggesting the existence of a rate-limiting step in progeny virus production.
ABSTRACT Although viral protein expression and progeny virus production were independently shown to be highly heterogeneous in individual cells, their direct relationship, analyzed by considering their heterogeneities, has not been investigated to date. To elucidate the direct relationship between viral protein expression and progeny virus production, we constructed a reporter herpes simplex virus 1 (HSV-1) by tagging Venus to the late protein Us11. We then separated the HSV-1-infected cell population into multiple subpopulations according to the fluorescence intensity of Venus—which reflected the expression of L proteins, largely constituting virion structural proteins—and titrated virus yields and performed electron microscopic analysis in each subpopulation. Our results revealed that infectious progeny virus production, as well as nucleocapsid maturation, was triggered only when L protein expression exceeded a specific threshold. This suggested the existence of a rate-limiting step in progeny virus production, with nucleocapsid maturation potentially being one such step.IMPORTANCEEarlier single-cell studies of virus-infected cells have revealed high heterogeneity in the state of viral gene expression and progeny virus yield. Notably, these two aspects have been shown independently, and therefore, the direct relationship between progeny virus production and viral gene expression has been unclear. This study, for the first time, demonstrated the direct and quantitative relationship between viral protein expression and progeny virus production by taking into account their heterogeneities and revealed a threshold for the levels of herpes simplex virus 1 protein expression for progeny virus production, thereby suggesting the existence of a rate-limiting step in progeny virus production.
Although viral protein expression and progeny virus production were independently shown to be highly heterogeneous in individual cells, their direct relationship, analyzed by considering their heterogeneities, has not been investigated to date. To elucidate the direct relationship between viral protein expression and progeny virus production, we constructed a reporter herpes simplex virus 1 (HSV-1) by tagging Venus to the late protein Us11. We then separated the HSV-1-infected cell population into multiple subpopulations according to the fluorescence intensity of Venus-which reflected the expression of L proteins, largely constituting virion structural proteins-and titrated virus yields and performed electron microscopic analysis in each subpopulation. Our results revealed that infectious progeny virus production, as well as nucleocapsid maturation, was triggered only when L protein expression exceeded a specific threshold. This suggested the existence of a rate-limiting step in progeny virus production, with nucleocapsid maturation potentially being one such step.IMPORTANCEEarlier single-cell studies of virus-infected cells have revealed high heterogeneity in the state of viral gene expression and progeny virus yield. Notably, these two aspects have been shown independently, and therefore, the direct relationship between progeny virus production and viral gene expression has been unclear. This study, for the first time, demonstrated the direct and quantitative relationship between viral protein expression and progeny virus production by taking into account their heterogeneities and revealed a threshold for the levels of herpes simplex virus 1 protein expression for progeny virus production, thereby suggesting the existence of a rate-limiting step in progeny virus production.Although viral protein expression and progeny virus production were independently shown to be highly heterogeneous in individual cells, their direct relationship, analyzed by considering their heterogeneities, has not been investigated to date. To elucidate the direct relationship between viral protein expression and progeny virus production, we constructed a reporter herpes simplex virus 1 (HSV-1) by tagging Venus to the late protein Us11. We then separated the HSV-1-infected cell population into multiple subpopulations according to the fluorescence intensity of Venus-which reflected the expression of L proteins, largely constituting virion structural proteins-and titrated virus yields and performed electron microscopic analysis in each subpopulation. Our results revealed that infectious progeny virus production, as well as nucleocapsid maturation, was triggered only when L protein expression exceeded a specific threshold. This suggested the existence of a rate-limiting step in progeny virus production, with nucleocapsid maturation potentially being one such step.IMPORTANCEEarlier single-cell studies of virus-infected cells have revealed high heterogeneity in the state of viral gene expression and progeny virus yield. Notably, these two aspects have been shown independently, and therefore, the direct relationship between progeny virus production and viral gene expression has been unclear. This study, for the first time, demonstrated the direct and quantitative relationship between viral protein expression and progeny virus production by taking into account their heterogeneities and revealed a threshold for the levels of herpes simplex virus 1 protein expression for progeny virus production, thereby suggesting the existence of a rate-limiting step in progeny virus production.
Although viral protein expression and progeny virus production were independently shown to be highly heterogeneous in individual cells, their direct relationship, analyzed by considering their heterogeneities, has not been investigated to date. To elucidate the direct relationship between viral protein expression and progeny virus production, we constructed a reporter herpes simplex virus 1 (HSV-1) by tagging Venus to the late protein Us11. We then separated the HSV-1-infected cell population into multiple subpopulations according to the fluorescence intensity of Venus—which reflected the expression of L proteins, largely constituting virion structural proteins—and titrated virus yields and performed electron microscopic analysis in each subpopulation. Our results revealed that infectious progeny virus production, as well as nucleocapsid maturation, was triggered only when L protein expression exceeded a specific threshold. This suggested the existence of a rate-limiting step in progeny virus production, with nucleocapsid maturation potentially being one such step.
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
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Issue 6
Keywords herpes simplex virus
rate-limiting step for virus production
heterogeneity of infection
Language English
License This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. https://creativecommons.org/licenses/by/4.0
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The authors declare no conflict of interest.
Moeka Nobe and Yuhei Maruzuru contributed equally to this article. The authors are listed in order of increasing seniority.
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Snippet Earlier single-cell studies of virus-infected cells have revealed high heterogeneity in the state of viral gene expression and progeny virus yield. Notably,...
Although viral protein expression and progeny virus production were independently shown to be highly heterogeneous in individual cells, their direct...
ABSTRACT Although viral protein expression and progeny virus production were independently shown to be highly heterogeneous in individual cells, their direct...
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SubjectTerms Animals
Cell Line
Chlorocebus aethiops
Gene Expression Regulation, Viral
Genes, Reporter
herpes simplex virus
Herpesvirus 1, Human - genetics
Herpesvirus 1, Human - physiology
heterogeneity of infection
Humans
Nucleocapsid - metabolism
rate-limiting step for virus production
Research Article
Vero Cells
Viral Proteins - biosynthesis
Viral Proteins - genetics
Viral Proteins - metabolism
Virology
Virus Replication
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Title Direct relationship between protein expression and progeny yield of herpes simplex virus 1
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