**6. Regulation of virus invasion**

Virus invasion does not uniformly occur in plant cultivars. Invasion efficiency varies between virus strains and between various cultivars [15]. Introducing dominant resistance by introgression allows the production of cultivars resistant to virus infection. The R genes (nucleotide binding-site leucine-rich repeat, NB-LRR) so introduced confer the resistance [22]. The *N* gene in *Nicotiana glutinosa*, *Tm* gene in tomatoes, and *L* gene in pepper plants are the known R genes for *Tobamovirus* infection. However, virus strains that overcame these resistance genes have evolved. The R genes induce hypersensitive response (HR) that limits the virus movement to the inoculation area [22]. Metabolic accumulation of salicylic acid, reactive oxygen species, and Ca2+ is characteristic to the HR response. Proteolysis through the ubiquitin pathway occurs, and induced caspase-like proteinases cause local cell death [22, 111]. In the case of *N* NB-LRR gene, translational arrest is involved [112]. The helicase domain of the replicase protein, MP, and CP is the avr proteins that elicit the HR of *N*, *Tm*, and *L* genes, respectively [22].

A new approach that introduces resistance may circumvent the resistance braking tobamoviruses. The clustered regularly interspaced short palindromic repeats (CRISPR-Cas) system is mutagenesis targeted by guide RNAs [113, 114]. The specific guide RNA has sequence homology to a desired DNA site, thus enabling the use of the CRISPR-Cas system to edit specific genome sites. Editing occurs by the introduction of double-stranded DNA breaks by the endonuclease Cas9 at a locus of interest while exploiting cellular repair mechanisms to cause high fidelity heritable genome sequence changes [113, 115]. Successful application of the Cas9 methodology was reported for the virus genera: *Geminivirus* [116], *Potyvirus*, and *Ipomovirus* [117].

The viral MP is a target for various regulatory events. During viral passage through PD, the MP is transiently synthesized, and it is degraded by 26S proteasome [118]. MP binding to viral RNA is associated with repression of viral RNA translation [119]. Phosphorylation of MP apparently has diverse regulatory consequences for MP. Phosphorylated MP no longer represses RNA translation [120], which may indicate temporal regulation of viral movement and synthesis. Kinases that phosphorylate the MP carboxy terminus stabilize the protein and promote its activity on PD dilation [73]. Interestingly the carboxy terminus of MP is susceptible to phosphorylation by the host cell wall-associated protein kinase that may be sequestering the MP to the cell wall [121]. Phosphorylation of ToMV MP at serine 37 apparently confers stabilization to the protein and is essential for its intracellular localization [122].

Suppression of posttranscriptional gene silencing (PTGS) is apparently an elementary mechanism for viral spread. Viruses are initiators of the endogenous PTGS, which degrades RNA. The viral RNA is processed into small interfering RNA (siRNA) by a drosophila Dicerlike enzyme, which is then incorporated into RNA-induced silencing complex (RISK) that degrades RNAs with sequence similarity to the siRNAs. A silencing signal, which may be the siRNAs, spreads between cells via PD and phloem [123]. This signal spread can be prevented by TMV [124]. Study of ToMV suppression of PTGS showed accumulation of siRNAs, suggested to indicate a block in PTGS downstream of siRNA production [125].

As mentioned above, indirect pathway to seed invasion is limited by meristematic exclusion. In addition, seeds apparently have an intrinsic inhibitory effect on virus infection [126].
