Cauliflower mosaic virus transactivator protein (TAV) can suppress nonsense-mediated decay by targeting VARICOSE, a scaffold protein of the decapping complex

Abstract

During pathogenesis, viruses hijack the host cellular machinery to access molecules and sub-cellular structures needed for infection. We have evidence that the multifunctional viral translation transactivator/viroplasmin (TAV) protein from Cauliflower mosaic virus (CaMV) can function as a suppressor of nonsense-mediated mRNA decay (NMD). TAV interacts specifically with a scaffold protein of the decapping complex VARICOSE (VCS) in the yeast two-hybrid system, and co-localizes with components of the decapping complex in planta. Notably, plants transgenic for TAV accumulate endogenous NMD-elicited mRNAs, while decay of AU-rich instability element (ARE)-signal containing mRNAs are not affected. Using an agroinfiltration-based transient assay we confirmed that TAV specifically stabilizes mRNA containing a premature termination codon (PTC) in a VCS-dependent manner. We have identified a TAV motif consisting of 12 of the 520 amino acids in the full-length sequence that is critical for both VCS binding and the NMD suppression effect. Our data suggest that TAV can intercept NMD by targeting the decapping machinery through the scaffold protein VARICOSE, indicating that 5′-3′ mRNA decapping is a late step in NMD-related mRNA degradation in plants.

The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay

“…Viral proteins from HTLV-1, MHV, ZIKV, HCV, and CaMV confer NMD resistance by directly targeting NMD or RNA decay factors (e.g., UPF1 or the EJC) (15,16,25,29,30). However, evidence of viral proteins directly binding to viral (or nonviral) transcripts and conferring NMD resistance is limited.…”

“…The viral core protein of Hepatitis C virus (HCV) disrupts the interaction between host protein WIBG and EJC components, attenuating NMD (29). Finally, the Cauliflower mosaic virus (CaMV) transactivator (TAV) protein interferes with the VARICOSE decapping complex, which is likely required late in the plant NMD pathway (30).…”

The cucumber mosaic virus 1a protein regulates interactions between the 2b protein and ARGONAUTE 1 while maintaining the silencing suppressor activity of the 2b protein

“…To further investigate the ability of the 1a protein to inhibit the 2b-AGO1 interaction, we carried Complexes of the cucumber mosaic virus 1a and 2b proteins co-localize with two P-body markers. Constructs encoding either of the fluorescently tagged P-body marker proteins DCP1-RFP or DCP2-RFP [76] were expressed in N. benthamiana leaves by agroinfiltration either alone (A, B), or in leaves co-infiltrated with split YFP fusions for the CMV 1a and 2b proteins (C, D). Confocal laser scanning microscopy was used to observe the localization of DCP1-RFP and DCP2-RFP, and the YFP signal from complexes formed between sYFPn-1a and sYFPc-2b.…”

The Complex Relationship between HTLV-1 and Nonsense-Mediated mRNA Decay (NMD)

“…The strength of these countermeasures shows the size of the threat that NMD constitutes for viral replication and the place of NMD among the cellular antiviral function. Those conclusions are also supported by comparison with several other viruses, especially retroviruses and (+) RNA viruses, which RNAs are also targeted by NMD and that evolved protective means [33,[35][36][37][39][40][41][42][43]87,[125][126][127]. It is important to note that the viruses that develop a trans-inhibition process against NMD, such as HTLV-1 and potentially HIV, might only protect themselves progressively; before the viral inhibitor is expressed at an adequate level and while viral mRNA are at low level during the early phase of infection, the NMD would inhibit optimal viral replication as demonstrated with the mouse hepatitis virus (MHV, a prototypic member of the betacoronaviridae, as SARS-CoV and MERSCoV), the plant virus potato virus X (alfaflexiviridae) and turnip crinkle virus (Tombusviridae) [37,39].…”

“…The nonsense-mediated mRNA decay (NMD) pathway is an interferon (IFN) independent process that has been recently demonstrated by convergent studies to degrade several viral RNA [33][34][35][36][37][38][39][40][41], hence it can be considered as an antiviral process as well. Concerning HTLV-1, it was shown that NMD inhibition led to an upregulation in the steady state levels of all viral mRNAs, revealing a direct and/or indirect sensitivity to NMD [42].…”