Exploration of Plant Virus Replication Inside a Surrogate Host, Saccharomyces cerevisiae, Elucidates Complex and Conserved Mechanisms

Sasvari, Zsuzsanna; Nagy, Peter D.

doi:10.1007/978-3-319-32919-2_2

Cited by 2 publications

(6 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genetic characterization showed that the antiviral phospholipid transporters acted to enhance the amplification of both the viral siRNAs and the endogenous virusactivated siRNAs by RDR6 and/or RDR1. Our findings suggest that the synthesis of dsRNA precursors of the viral and host siRNAs by the cellular RDRs may require subcellular membrane enrichment of specific phospholipids known to be necessary for the formation of vesicle-like membrane invaginations during RNA replication of positive-strand RNA viruses (40,41).…”

Section: Significancementioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

“…Much is known about the mechanism of RNA synthesis by the RdRPs of plant and animal positive-strand RNA viruses (40,41). For example, brome mosaic virus and tomato bushy stunt virus genomic RNAs replicate inside vesicle-like membrane invaginations (known as spherules) of the endoplasmic reticulum (ER) and peroxisomes, respectively (40,41). The formation of these spherules is induced in the infected cell after the recruitment of the viral RdRP and host factors to the subcellular membrane microdomains and is correlated with the enrichment of specific phospholipids at the replication sites (51,52).…”

Section: Discussionmentioning

confidence: 99%

“…Similar to vasiRNAs, vsiRNAs are also highly abundant and can amount to up to 30% of the total small RNAs in infected plants (15,16). Thus, it is possible that only the synthesis of dsRNA precursors of the highly abundant vsiRNAs and vasiRNAs may require the extensive membrane reorganization to form spherules analogous to those for virus RNA replication (40,41).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Lipid flippases promote antiviral silencing and the biogenesis of viral and host siRNAs in Arabidopsis

Guo

Lü

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Dicer-mediated processing of virus-specific dsRNA into short interfering RNAs (siRNAs) in plants and animals initiates a specific antiviral defense by RNA interference (RNAi). In this study, we developed a forward genetic screen for the identification of host factors required for antiviral RNAi in Arabidopsis thaliana. Using whole-genome sequencing and a computational pipeline, we identified aminophospholipid transporting ATPase 2 (ALA2) and the related ALA1 in the type IV subfamily of P-type ATPases as key components of antiviral RNAi. ALA1 and ALA2 are flippases, which are transmembrane lipid transporter proteins that transport phospholipids across cellular membranes. We found that the ala1/ala2 single-and double-mutant plants exhibited enhanced disease susceptibility to cucumber mosaic virus when the virus-encoded function to suppress RNAi was disrupted. Notably, the antiviral activity of both ALA1 and ALA2 was abolished by a single amino acid substitution known to inactivate the flippase activity. Genetic analysis revealed that ALA1 and ALA2 acted to enhance the amplification of the viral siRNAs by RNA-dependent RNA polymerase (RdRP) 1 (RDR1) and RDR6 and of the endogenous virus-activated siRNAs by RDR1. RNA virus replication by plant viral RdRPs occurs inside vesicle-like membrane invaginations induced by the recruitment of the viral RdRP and host factors to subcellular membrane microdomains enriched with specific phospholipids. Our results suggest that the phospholipid transporter activity of ALA1/ALA2 may be necessary for the formation of similar invaginations for the synthesis of dsRNA precursors of highly abundant viral and host siRNAs by the cellular RdRPs.

show abstract

Section: Significancementioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Lipid flippases promote antiviral silencing and the biogenesis of viral and host siRNAs in Arabidopsis

Guo

Lü

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Some host proteins play a permissive role for viral infection and some play a restrictive role (''proviral'' and ''antiviral'' factors, respectively). There are abundant proviral factors as shown by recent studies (Friedel and Haas, 2011;Wang, 2015;Enard et al, 2016;Wilke and Sawyer, 2016;Sasvari and Nagy, 2016) thus pointing to many potential targets for resistance engineering. Very recent work has used gene-editing methodologies to suppress (knock out or render non-functional) proviral factors and achieve resistance (Chandrasekaran et al, 2016;Pyott et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance

et al. 2017

View full text Add to dashboard Cite

Proviral factors are host proteins hijacked by viruses for processes essential for virus propagation such as cellular entry and replication. Pathogens and their hosts co-evolve. It follows that replacing a proviral factor with a functional ancestral form of the same protein could prevent viral propagation without fatally compromising organismal fitness. Here, we provide proof of concept of this notion. Thioredoxins serve as general oxidoreductases in all known cells. We report that several laboratory resurrections of Precambrian thioredoxins display substantial levels of functionality within Escherichia coli. Unlike E. coli thioredoxin, however, these ancestral thioredoxins are not efficiently recruited by the bacteriophage T7 for its replisome and therefore prevent phage propagation in E. coli. These results suggest an approach to the engineering of virus resistance. Diseases caused by viruses may have a devastating effect in agriculture. We discuss how the suggested approach could be applied to the engineering of plant virus resistance.

show abstract

Exploration of Plant Virus Replication Inside a Surrogate Host, Saccharomyces cerevisiae, Elucidates Complex and Conserved Mechanisms

Cited by 2 publications

References 119 publications

Lipid flippases promote antiviral silencing and the biogenesis of viral and host siRNAs in Arabidopsis

Lipid flippases promote antiviral silencing and the biogenesis of viral and host siRNAs in Arabidopsis

Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance

Contact Info

Product

Resources

About