The economic stakes are enormous. Reported yield losses in tomato and cucurbit crops range from 80 to 100 percent depending on the growth stage at infection, the host genotype, and the severity of the epidemic. The virus now infects more than 40 plant species across several families, including Solanaceae, Cucurbitaceae, Fabaceae, Malvaceae, Euphorbiaceae, and Papaveraceae. Its arrival in Spain in 2012 marked a major epidemiological shift, as it rapidly adapted to cucurbit crops such as zucchini and melon and then spread throughout the Mediterranean to Italy, Tunisia, Morocco, Greece, Algeria, France, and Portugal. Wild and weed species, including Datura stramonium, Solanum nigrum, and Sonchus oleraceus, serve as reservoirs that keep viral inoculum alive between growing seasons and seed new outbreaks.

At the molecular level, ToLCNDV carries a bipartite circular single-stranded DNA genome composed of two molecules, DNA-A and DNA-B, each roughly 2.7 to 2.8 kilobases long. DNA-A encodes the replication-associated protein Rep/AC1, the transcriptional activator protein TrAP/AC2, the replication enhancer protein REn/AC3, the coat protein CP/AV1, and the AC4 protein. DNA-B encodes the nuclear shuttle protein NSP/BV1, which ferries viral DNA between the nucleus and cytoplasm, and the movement protein MP/BC1, which enables cell-to-cell passage through plasmodesmata. This compact, overlapping genome organization allows the virus to hijack host cell resources with remarkable efficiency, including cell cycle regulation and antiviral defense responses. Notably, in the presence of a DNA β satellite, the DNA-A component can act in a monopartite-like manner, with the satellite-encoded βC1 protein complementing the movement functions normally provided by DNA-B.

The virus population itself is far from homogeneous. Asian isolates cluster in a group designated ToLCNDV-OM, the Oriental melon strain, with approximately 94 percent DNA-A sequence identity among them. Isolates from the western Mediterranean Basin form a distinct and highly homogeneous group, ToLCNDV-ES, the Spain strain, sharing more than 99 percent identity among themselves but less than 94 percent with other global isolates. Isolates from India and Pakistan show further divergence, and current data suggest the ToLCNDV population comprises at least seven genetically distinct strains. Comparative transcriptomic studies indicate that Indian isolates induce stronger host transcriptional reprogramming and more severe disease responses than ToLCNDV-ES isolates in cucumber, hinting at strain-specific differences in virulence and resistance-breaking potential, though definitive evidence for strain-specific resistance breakdown remains limited.

Transmission biology adds another layer of complexity. Viruliferous whiteflies acquire viral particles through their stylets within 10 to 60 minutes of feeding on phloem tissues. After a latent period inside the vector, typically 8 to 19 hours depending on virus and vector species, the virus follows a circulative path from the midgut epithelium into the hemolymph and finally to the salivary glands, where it is injected into a new host during subsequent feeding. Experimental studies have also detected seed and pollen transmission, with high transmission rates of 60 percent to seedlings reported in zucchini, raising phytosanitary concerns about seed movement, although another report suggests seed transmission is unlikely to impact natural field conditions significantly.

Host resistance remains the most cost-effective and environmentally friendly approach to managing begomovirus-induced leaf curl disease. In tomato, the dominant Ty gene family, derived primarily from wild Solanum species such as S. chilense, S. peruvianum, S. habrochaites, and S. pimpinellifolium, provides the primary source of resistance. Ty-1 and Ty-3 encode DFDGD-class RNA-dependent RNA polymerases that enhance RNA-directed DNA methylation and transcriptional gene silencing, thereby inhibiting viral replication through increased cytosine methylation of viral genomes. Ty-2, by contrast, functions through nucleotide-binding leucine-rich repeat-mediated immune reactions. The recessive allele ty-5 corresponds to a mutation in the pelota gene, which affects translation and viral replication efficiency. In cucurbits, resistance is typically polygenic and quantitative. The recently identified Cy-1 locus on cucumber chromosome 1 encodes CsRDR3, a DFDGD-class RNA-dependent RNA polymerase functionally homologous to Ty-1 and Ty-3 in tomato, and functional silencing of CsRDR3 severely compromises resistance, confirming its antiviral role. Melon resistance is associated with major quantitative trait loci on chromosomes 11, 2, and 12, while pumpkin resistance loci on chromosomes 7 and 8 show molecular marker prediction accuracies approaching 94 percent.

Yet the virus has evolved sophisticated counter-defenses. Several ToLCNDV-encoded proteins, including AV2, AC2, AC4, and the satellite-associated βC1, function as viral suppressors of RNA silencing. AC2 is a central regulator that suppresses both post-transcriptional and transcriptional gene silencing, obstructing components of the DNA methylation pathway such as ARGONAUTE 4 and interfering with AGO1-mediated RISC activity. AC4 binds small RNAs and prevents their integration into the RISC complex, while AV2 interferes with RDR1-mediated antiviral siRNA amplification. The virus also manipulates host transcription and hormone networks, particularly jasmonic acid and ethylene signaling, compromising plant immunity. Variations in a 63-nucleotide region of the C-terminal domain of TrAP and REn alter interactions with host proteins such as PCNA and AGO1, regulating infection efficiency and facilitating host range changes. Interactions with betasatellites significantly increase viral DNA accumulation and accelerate disease development, with viral titers correlating more strongly with betasatellite abundance than with the helper virus itself, while alphasatellites operate more subtly, often attenuating symptoms and reducing betasatellite accumulation through competitive dynamics within the virus-satellite complex.

Emerging technologies offer new hope for durable control. CRISPR/Cas systems can be designed to target conserved viral sequences essential for replication or pathogenicity. Early demonstrations in transgenic Nicotiana benthamiana and Arabidopsis thaliana expressing Cas9 with guide RNAs targeting viral intergenic regions, coat protein genes, or Rep genes showed marked reductions in viral accumulation and symptom severity. A recent study targeting Chilli leaf curl virus in Nicotiana benthamiana found that dual-guide constructs consistently outperformed single-guide systems, with the most effective combination reducing viral titer by 49.3 percent at 4 days post-inoculation and 47.9 percent at 20 days post-inoculation. Cas12a, which generates staggered cuts and processes multiplex guide arrays more efficiently than Cas9, presents another promising avenue. Beyond direct viral targeting, editing host susceptibility genes implicated in replication or intracellular trafficking may offer recessive, broad-spectrum resistance. RNA silencing-based strategies, including host-induced gene silencing and spray-induced gene silencing with exogenous double-stranded RNA molecules targeting viral genes such as Rep or AC2, have lowered viral titers by 40 to 80 percent in related plant-virus systems, offering a non-transgenic crop protection approach.

Despite these advances, sustainable management remains challenging due to the rapid evolution of the virus and the adaptability of its vector. Strong selection pressure from resistant cultivars can drive the emergence of resistance-breaking viral types, and relying on host resistance alone may not provide long-term defense. The whitefly B. tabaci is itself a cryptic species complex, with different members varying in transmission efficiency, insecticide resistance, fecundity, and climatic adaptability, complicating regional disease forecasting. Climate change adds further complexity, as milder winters, increased protected horticulture, and temperature fluctuations favor whitefly population growth and prolong transmission periods, likely promoting earlier seasonal outbreaks and expansion into historically unsuitable regions.

The future of ToLCNDV management, the review concludes, will rest on integrated approaches combining resistant cultivars, certified clean seed, rapid molecular diagnostics such as PCR and LAMP assays, judicious whitefly control, management of alternate weed hosts, crop sanitation, and coordinated area-wide surveillance. Multi-omics integration, spanning genomics, transcriptomics, proteomics, metabolomics, epigenomics, and small RNA sequencing, can generate systems-level models of susceptibility and resistance, while single-cell and spatial transcriptomics may reveal tissue-specific defense niches in phloem-associated cells where begomoviruses replicate and move. Artificial intelligence and machine learning tools are emerging for outbreak prediction, symptom recognition, and accelerated breeding decisions. Translating molecular discoveries into successful field control will require sustained commitment, continuous vigilance, and a systems-level understanding of the host-virus-vector relationship under changing climatic and agricultural conditions.

Subject of Research: Virology

Article Title: Host resistance and susceptibility to tomato leaf curl New Delhi virus: molecular mechanisms, genetic resources, and strategies for durable control

Article References: Phogat, S., Shukla, G., Singh, A., Singhal, P., Singh, J., & Baranwal, V. K. (2026). Host resistance and susceptibility to tomato leaf curl New Delhi virus: molecular mechanisms, genetic resources, and strategies for durable control. Frontiers in Virology, 6, Article 1869978. https://doi.org/10.3389/fviro.2026.1869978

Image Credits: AI Generated

DOI: 10.3389/fviro.2026.1869978

Keywords: ToLCNDV, begomovirus, plant virology, host resistance, CRISPR, whitefly, RNA silencing, durable disease control, Host, resistance, susceptibility, tomato