PROTEIN DISULFIDE ISOMERASE LIKE 5-1 is a susceptibility factor to plant viruses

Protein disulfide isomerases (PDIs) catalyze the correct folding of proteins and prevent the aggregation of unfolded or partially folded precursors. Whereas suppression of members of the PDI gene family can delay replication of several human and animal viruses (e.g., HIV), their role in interactions with plant viruses is largely unknown. Here, using a positional cloning strategy we identified variants of PROTEIN DISULFIDE ISOMERASE LIKE 5–1 (HvPDIL5-1) as the cause of naturally occurring resistance to multiple strains of Bymoviruses. The role of wild-type HvPDIL5-1 in conferring susceptibility was confirmed by targeting induced local lesions in genomes for induced mutant alleles, transgene-induced complementation, and allelism tests using different natural resistance alleles. The geographical distribution of natural genetic variants of HvPDIL5-1 revealed the origin of resistance conferring alleles in domesticated barley in Eastern Asia. Higher sequence diversity was correlated with areas with increased pathogen diversity suggesting adaptive selection for bymovirus resistance. HvPDIL5-1 homologs are highly conserved across species of the plant and animal kingdoms implying that orthologs of HvPDIL5-1 or other closely related members of the PDI gene family may be potential susceptibility factors to viruses in other eukaryotic species.Infectious diseases caused by plant viruses threaten agricultural productivity and reduce globally attainable agricultural production by about 3% (1). In specific pathosystems, plant viruses can result in the loss of the entire crop. For example, the devastation of cassava production by cassava mosaic geminiviruses (CMGs) in Uganda during the 1990s led to widespread food shortages and famine-related deaths (2). Unfortunately protecting plants against viruses (especially soil-borne viruses) by using agrochemicals to control virus vectors is seldom efficient from economic or ecological perspectives. Therefore, crop protection based on naturally occurring virus resistance is key to minimizing losses and achieving sustainable crop yields.Positive-strand RNA viruses represent the largest group of plant viruses (3). They cause a very high proportion of the important infectious virus diseases in agriculture (4, 5). Such plant viruses carry a reduced genome that encodes a limited set of functional proteins (4–10 viral proteins)—insufficient to complete the entire virus replication and proliferation cycle (6). Instead, over evolutionary time, viruses recruited host factors to perform the infectious life cycle (7). This dependence on host factors establishes a possibility that plants can evolve escape, tolerance, or resistance mechanisms to ameliorate the consequences of viral infection. The absence of essential host factors could interfere with the infection process or restrict proliferation (8) leading to either mono- or polygenic recessive resistance (5). Prominent examples of such susceptibility factors that are conserved in multiple plant–virus systems are the EUKARYOTIC TRANSLATION INITIATION FACTORS (EIF)4E, iso4E, 4G, and iso4G (9). Translation initiation factors may interact directly with viral RNA where they catalyze the initiation of translation of viral polyproteins (10, 11). In addition, to establish replication and assembly complexes during infection, viruses typically create membrane-bound environments, referred to as “virus factories” (12). There, cellular chaperones such as HSP70 and DNAJ-like proteins likely contribute to the correct folding and translocation of substrates (12, 13). However, only a few such host factors are known (7, 9, 14).Barley yellow mosaic virus disease caused by barley yellow mosaic virus (BaYMV) and barley mild mosaic virus (BaMMV) (both belong to Bymoviruses) seriously threatens winter barley production in Europe and East Asia (4). Infection leads to yellow discoloration and stunted growth and may result in yield loss of up to 50% (15). Soil-borne transmission via the plasmodiophorid Polymyxa graminis prohibits plant protection by chemical measures, and breeding for resistant cultivars is therefore the only practicable way to prevent yield loss. The naturally occurring recessive resistance locus rym11 confers complete broad-spectrum resistance to all known European isolates of BaMMV and BaYMV (16–19). In the present study, we used a positional cloning strategy to identify the gene underlying rym11-based resistance. We show that it is a susceptibility factor belonging to a gene family of PROTEIN DISULFIDE ISOMERASES (PDIs), and is highly conserved across eukaryotic species. We observe a strong correlation between natural allelic variation and geographic distribution, suggesting that both the origin and subsequent adaptive selection for rym11-based resistance in winter barley occurred in East Asia.