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Researchers of the CReSA have demonstrated the relevance of the host nucleus during ASFV infection. These discoveries might have important implications when searching for antiviral strategies against ASF that is currently causing real economical problems in many sub-Saharan countries and knocking at the door of the EU.
In the present study, new evidences supporting the implication of the host nucleus during ASFV infection are provided. Thus, during the initial phase of ASFV replication, an early phosphorylation and disassembling of lamin A/C (a multifunctional protein localized both in the nuclear periphery and nucleoplasm of eukaryotic cells and involved in nuclear stability, chromatin structure and gene expression) was detectable, coinciding with the sites where the newly synthesized ASFV DNA was found. This early phosphorylation and disassembling of lamin A/C might facilitate the interaction of ASFV DNA with nuclear proteins required for proper viral DNA conformation and/or initiation of the replication process, as it has been previously reported for other nuclear viruses such as herpesviruses.
At late times post-infection, the nascent ASFV DNA, the lamin A/C and nucleoporin p62 (another nuclear marker) were also found within the cytoplasm of the infected cells (Figure 1), pointing towards some kind of budding-like mechanism of the ASFV DNA from the nucleus to the cytoplasm of the infected cell.
On the other hand, intra-nuclear lamina, the SC-35marker (specifically labelling the splicing speckles) and the RNA pol II redistributed in enlarged foci within the nucleoplasm of the ASFV infected cells from very early after the infection; a picture previously described for no-infected cells in the presence of transcription inhibitors. Western blot analysis with antibodies that recognize different forms of the RNA pol II allowed to confirm that early after ASFV infection the RNA pol II was hypophosphorylated to be finally degraded at late times post-infection.
All together these results indicate a possible mechanism to block the cellular transcription early during viral infection, contributing to the cellular shut-off described during the ASFV infection.
Our results clearly demonstrate that nuclear interactions during infection with ASFV are more important than previously believed.
Ballester M, Rodríguez-Cariño C, Pérez M, Gallardo C, Rodríguez JM, Salas ML, Rodriguez F. Implication of the host nucleus during African swine fever virus (ASFV) infection. CReSA. Spain.
http://www.cresa.es
