Screenshot 2018-04-16 09.30.57Nesta segunda-feira, dia 16 de abril de 2017, as 16 h na sala de reuniões do DFP, será transmitido por videoconferência o Seminário “The Actin Network Facilitates the Recruitment of the ATP Generating Glycolytic Enzyme PGK1 into the Viral Replicase Complex“, a ser apresentado pelo estudante de doutorado da U.K. Ms. Melissa Molho, orientado do Prof. Peter Nagy da University of Kentucky.

Abstract

Plus-stranded RNA viruses hijack cellular components and pathways to replicate and propagate inside the cell. Tombusviruses use the actin network to modulate cells dynamics and regulate viral replication. p33 viral replication protein of Tomato bushy stunt virus (TBSV) interacts with cellular cofilin, an actin depolymerization factor. Disruption of cofilin in yeast (Saccharomyces cerevisiae) inhibits the dynamics of the actin network and increases viral replication. TBSV recruits host proteins and lipids through the exploitation of the actin network (Nawaz-Ul-Rehman et al., 2016). Co-purification-based proteomic approaches using temperature sensitive (ts) Actin (Act1) mutant yeasts showed altered efficiency of recruitment of pro-viral and restriction host factors into the Viral Replication Compartment (VRC) in comparison with wild type yeast.  Modification of the host actin network dynamics induces viral replication as well as increasing energy requirements inside the VRC. TBSV replication protein p33 co-opts the glycolytic enzyme phosphoglycerate kinase (PGK1), which catalyzes the conversion of ADP to ATP. PGK1 facilitates the assembly of the VRC and supplies the fuel requirements inside the replication compartments (Prasanth, Chuang, & Nagy, 2017). Thus, ATP levels were compared between wild-type yeast and tsAct1 mutants. Employing, FRET-based ATP detection our actin mutant (tsAct1) showed higher ATP generation inside of the replication compartment to that of the wild type. Furthermore, we created a yeast tsAct1 mutant with inducible PGK1 expression; depletion of PGK1 in this mutant significantly reduced viral accumulation, demonstrating that PGK1 has an essential role during TBSV replication. Finally, bacterial effectors that target the actin filaments and affect the dynamics of the actin network, also affect TBSV replication. These experiments have allowed us to increase our knowledge about the importance of the actin network in TBSV replication.

 

References

Nawaz-Ul-Rehman, M. S., Prasanth, K. R., Xu, K., Sasvari, Z., Kovalev, N., de Castro Martin, I. F., . . . Nagy, P. D. (2016). Viral Replication Protein Inhibits Cellular Cofilin Actin Depolymerization Factor to Regulate the Actin Network and Promote Viral Replicase Assembly. PLoS Pathog, 12(2), e1005440. doi:10.1371/journal.ppat.1005440

Prasanth, K. R., Chuang, C., & Nagy, P. D. (2017). Co-opting ATP-generating glycolytic enzyme PGK1 phosphoglycerate kinase facilitates the assembly of viral replicase complexes. PLoS Pathog, 13(10), e1006689. doi:10.1371/journal.ppat.1006689

 

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