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The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly


Cellular and viral life cycles are connected through multiple, though poorly understood, mechanisms. Parvoviruses infect humans and a broad spectrum of animals, causing a variety of diseases, but they are also used in experimental cancer therapy and serve as vectors for gene therapy. Parvoviruses can only multiply in proliferating cells providing essential replicative and transcriptional functions. However, it is unknown whether the cell cycle regulatory machinery may also control parvovirus assembly. We found that the nuclear translocation of parvovirus MVM capsid subunits (VPs) was highly dependent on physiological cell cycle regulations in mammalian fibroblasts, including: quiescence, progression through G1/S boundary, DNA synthesis, and cell to cell contacts. VPs nuclear translocation was significantly more sensitive to cell cycle controls than viral genome replication and gene expression. The results support nuclear capsid assembly as the major driving process of parvoviruses biological hallmarks, such as pathogenesis in proliferative tissues and tropism for cancer cells. In addition, disturbing the tight coupling of parvovirus assembly with the cell cycle may determine viral persistence in quiescent and post-mitotic host tissues. These findings may contribute to understand cellular regulations on the assembly of other nuclear eukaryotic viruses, and to develop cell cycle-based avenues for antiviral therapy.


Vyšlo v časopise: The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004920
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004920

Souhrn

Cellular and viral life cycles are connected through multiple, though poorly understood, mechanisms. Parvoviruses infect humans and a broad spectrum of animals, causing a variety of diseases, but they are also used in experimental cancer therapy and serve as vectors for gene therapy. Parvoviruses can only multiply in proliferating cells providing essential replicative and transcriptional functions. However, it is unknown whether the cell cycle regulatory machinery may also control parvovirus assembly. We found that the nuclear translocation of parvovirus MVM capsid subunits (VPs) was highly dependent on physiological cell cycle regulations in mammalian fibroblasts, including: quiescence, progression through G1/S boundary, DNA synthesis, and cell to cell contacts. VPs nuclear translocation was significantly more sensitive to cell cycle controls than viral genome replication and gene expression. The results support nuclear capsid assembly as the major driving process of parvoviruses biological hallmarks, such as pathogenesis in proliferative tissues and tropism for cancer cells. In addition, disturbing the tight coupling of parvovirus assembly with the cell cycle may determine viral persistence in quiescent and post-mitotic host tissues. These findings may contribute to understand cellular regulations on the assembly of other nuclear eukaryotic viruses, and to develop cell cycle-based avenues for antiviral therapy.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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