Cytoplasmic factories, virus assembly, and DNA replication kinetics collectively constrain the formation of poxvirus recombinants
| Autor: | Mira M. Shenouda, Y-C James Lin, Ryan S. Noyce, Quinten Kieser, David H. Evans |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Endoplasmic Reticulum
Biochemistry law.invention chemistry.chemical_compound Cytosol law Electron Microscopy Energy-Producing Organelles Recombination Genetic Microscopy 0303 health sciences Multidisciplinary 030302 biochemistry & molecular biology Chemical Reactions Recombination Reactions Recombinant Proteins Mitochondria Cell biology Nucleic acids Chemistry Virion assembly Physical Sciences Recombinant DNA Medicine Cellular Structures and Organelles Recombination Research Article DNA Replication DNA recombination Science Vaccinia virus Viral Structure Bioenergetics Biology Research and Analysis Methods Microbiology Cell Line 03 medical and health sciences Virology Genetics Animals Viroplasm 030304 developmental biology Biology and life sciences Virus Assembly Virion DNA replication Proteins DNA Cell Biology Viral Replication Viral replication chemistry DNA Viral Transmission Electron Microscopy Vaccinia |
| Zdroj: | PLoS ONE, Vol 15, Iss 1, p e0228028 (2020) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Poxviruses replicate in cytoplasmic structures called factories and each factory begins as a single infecting particle. Sixty-years ago Cairns predicted that this might have effects on vaccinia virus (VACV) recombination because the factories would have to collide and mix their contents to permit recombination. We've since shown that factories collide irregularly and that even then the viroplasm mixes poorly. We’ve also observed that while intragenic recombination occurs frequently early in infection, intergenic recombination is less efficient and happens late in infection. Something inhibits factory fusion and viroplasm mixing but what is unclear. To study this, we’ve used optical and electron microscopy to track factory movement in co-infected cells and correlate these observations with virus development and recombinant formation. While the technical complexity of the experiments limited the number of cells that are amenable to extensive statistical analysis, these studies do show that intergenic recombination coincides with virion assembly and when VACV replication has declined to ≤10% of earlier levels. Along the boundaries between colliding factories, one sees ER membrane remnants and other cell constituents like mitochondria. These collisions don't always cause factory fusion, but when factories do fuse, they still entrain cell constituents like mitochondria and ER-wrapped microtubules. However, these materials wouldn’t seem to pose much of a further barrier to DNA mixing and so it’s likely that the viroplasm also presents an omnipresent impediment to DNA mixing. Late packaging reactions might help to disrupt the viroplasm, but packaging would sequester the DNA just as the replication and recombination machinery goes into decline and further reduce recombinant yields. Many factors thus appear to conspire to limit recombination between co-infecting poxviruses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |