Viruses are among the most devastating microorganisms across all kingdoms of life, posing serious threats to human and animal health and causing massive crop losses (Rao & Reddy, 2020). One of the most defining features of viral agents is their limited genetic information, which often falls several orders of magnitude below those of the hosts they rely on to survive. Despite this apparently unbalanced situation, viruses are, as obligatory intracellular parasites, able to subdue the host metabolism for their own benefit, just as if it were the case of David meeting Goliath. To achieve this fruitful result, viruses have evolved a vast array of mechanisms for strategically hijacking and/or subverting host resources to thrive. The host, on its side, deploys diverse countermeasures to prevent or limit the progress of viral infection, which, in turn, are targeted by the virus to avoid being defeated (Medina-Puche and Lozano-Duran, 2019, Ramage and Cherry, 2015). Still, the host may activate counter-counter defense mechanisms to cope with virus trickery. The outcome of this never-ending war may be variable and can go from non-infection (when the virus is incapable to overcome defenses mounted by the host or there is incompatibility with the host factors) to a highly productive infection which, moreover, may cause, sometimes fatal, host disease (Fermin, 2018, García and Pallás, 2015).

Focusing the attention on plants, these organisms have developed a plethora of mechanisms to fight off viruses, some of which are continuously operative as physical barriers (e.g., waxy cuticles, cell walls) or passive resistance (e.g., lack of components required for virus life cycle), whereas others will be induced upon pathogen attack (Marwal & Gaur, 2020). Of special relevance in this context is RNA silencing, an evolutionarily conserved mechanism in eukaryotes that mediates sequence-specific regulation of gene expression through the action of small RNAs (sRNAs), including microRNAs (miRNAs) and small interfering RNAs (siRNAs), which are stabilized by 2′-O-methylation at their 3′ ends catalyzed by the methyltransferase HEN1. In the last two decades, intensive investigations have highlighted the role of RNA silencing in viral clearance, particularly in plants where it has been equated with the immune system of animals (Lopez-Gomollon & Baulcombe, 2022). The antiviral RNA silencing is triggered by double-stranded (ds) RNAs of viral origin (e.g., replication intermediates or self-complementary stretches in viral RNAs) that are processed by RNase III Dicer-like (DCL) enzymes generating primary siRNAs with a size of 21–24 nucleotides. One of the strands of these small duplexes is incorporated into an effector complex known as RISC (RNA-induced silencing complex) that invariably contains an endonuclease of the Argonaute (AGO) family. RISC is then directed by the associated siRNA to a target RNA of complementary sequence, promoting its degradation or, in some cases, blocking its translation. The whole process may be strengthened by host RNA-dependent RNA polymerases (RDRs), which facilitate siRNA-primed generation of additional ssRNA templates from RISC-cleaved or other aberrant RNA products that are subsequently processed into secondary siRNAs by DCLs. Among host RDRs, RDR6 and its associated RNA-binding protein, suppressor of gene silencing 3 (SGS3), have been found to be particularly relevant for antiviral silencing, while among AGO proteins, AGO1 and AGO2 appear to function as the main effectors of the pathway. Notably, RNA silencing operates as a cell- and non-cell-autonomous process, with siRNAs serving as mobile signals that spread silencing from the initial infection site to distal tissues (Yang & Li, 2018). The importance of RNA silencing in the virus-host interplay is highlighted by the observation that essentially all plant viruses encode at least one protein able to counteract this host defense mechanism, the so-called viral suppressors of RNA silencing (VSRs). These proteins, which exhibit high variability at structural level, can block RNA silencing at different steps. Inhibiting dsRNA processing or sequestering sRNAs are common strategies employed by VSRs to prevent RISC assembly and block systemic silencing. In addition, direct or indirect interactions with key protein components of the silencing machinery may also contribute to their suppressive activity (Csorba et al., 2015, Jin et al., 2021).

In addition to the primary role of RNA silencing, other inducible defense mechanisms may contribute to plant antiviral immunity, including effector-triggered immunity (ETI), pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), non-sense mediated mRNA decay (NMD), resistance mediated by the ubiquitin–proteasome system (UPS), and hormone-regulated defense responses (Garcia-Ruiz, 2019, Lozano-Durán, 2024, Marwal and Gaur, 2020). Besides these mechanisms, in recent years autophagy has emerged as a major player in the arms race between plants and viruses, although our understanding of its role in this context is still limited (Kushwaha et al., 2019, Yang et al., 2020).

In this review, we summarize current knowledge on the dual role of autophagy in plant–virus interactions, highlighting its function both as a key component of plant defense responses and, alternatively, as a facilitator of viral infection. We also discuss potential future research directions, including key unanswered questions and possible biotechnological applications of manipulating the autophagy pathway to enhance crop resistance and overall plant health.