Plant DNA viruses — including double-stranded DNA viruses such as caulimoviruses and single-stranded DNA viruses such as geminiviruses — are devastating crop pathogens. Upon infection, their genomes are packaged with host histones into minichromosomes, where histone post-translational modifications (PTMs) play critical roles in both viral replication and host defense. Hosts can transcriptionally repress viral minichromosomes through these modifications; however, how viruses counteract this chromatin-based defense mechanism has remained largely unclear.

To address this question, a research team from the South China Botanical Garden of the Chinese Academy of Sciences, in collaboration with the Temasek Life Sciences Laboratory in Singapore, has shown that plant DNA viruses hijack the host deubiquitinases UBP12/13 through their pathogenicity factor P6, remodeling the epigenetic landscape of viral minichromosomes to relieve host epigenetic silencing and promote infection. The findings identify UBP12/13 as potential novel targets for engineering virus-resistant crops.

The study was published in PLOS Pathogens on Oct.15.

Using affinity purification–mass spectrometry (AP-MS), the researchers screened for host proteins that interact with the CaMV pathogenicity factor P6 and identified the Arabidopsis deubiquitinases UBP12 and UBP13 as prominent interactors. A series of assays — including yeast two-hybrid (Y2H), pull-down, co-immunoprecipitation (Co-IP), and bimolecular fluorescence complementation (BiFC) — confirmed that P6 directly interacts with UBP12 and UBP13 in the nucleus, through the MATH domain of the two deubiquitinases.

Genetic and phenotypic analyses showed that ubp12/13 mutants exhibited significantly enhanced resistance to CaMV, with delayed disease progression and markedly reduced accumulation of viral DNA and transcripts. By contrast, UBP12/13 overexpression lines displayed more severe symptoms and higher viral loads. Further functional validation demonstrated that the deubiquitinase activity of UBP12 is required for its pro-viral function: a catalytic-dead C/S mutant lost the ability to promote viral infection.

UBP12/13 are known to deubiquitinate monoubiquitinated H2A (H2Aub). Chromatin immunoprecipitation–qPCR (ChIP-qPCR) revealed that UBP12/13 specifically modulate the histone modification status at the viral 35S promoter, reducing the repressive marks H2Aub and H3K27me3 and thereby relieving transcriptional repression of the viral genome.

Importantly, the pathogenicity factor AC2 of the geminivirus Cabbage leaf curl virus (CaLCuV) also targets UBP12/13 in the nucleus, and ubp12/13 mutants showed enhanced resistance to CaLCuV. This indicates that hijacking UBP12/13 is a conserved infection strategy among diverse plant DNA viruses.

Based on these findings, the researchers propose a working model. In wild-type plants, the viral pathogenicity factor P6/AC2 enters the nucleus and interacts with UBP12/13, which remove H2Aub and reduce H3K27me3 levels at the 35S promoter of the viral minichromosome, alleviating host epigenetic silencing and enabling robust viral transcription and replication. In ubp12/13 loss-of-function mutants, elevated H2Aub and H3K27me3 persist at the 35S promoter, leading to sustained transcriptional repression of the virus and enhanced plant resistance. The study thus elucidates a previously unrecognized mechanism by which plant DNA viruses manipulate host epigenetic machinery to promote infection.

The study was supported by grants from the National Natural Science Foundation of China and the Guangdong Science and Technology Plan Project.

Proposed working model illustrating how CaMV P6 exploits UBP12/13 to alleviate host epigenetic silencing and promote viral infection. (Image by LI Shun)