Herman B. Scholthof was born in Kring van Dorth, Gorssel, the Netherlands, in 1959. He was raised on a farm and, after completing an agricultural college degree in plant research, he attended Wageningen University to obtain his B.S. degree, followed by an M.S. degree in 1986 in the Laboratory of Virology headed by Rob Goldbach. For his dissertation research at the University of Kentucky, he investigated gene expression of caulimoviruses with Bob Shepherd. After finishing his Ph.D. degree in 1990, he relocated to the University of California-Berkeley for post-doctoral studies on Tomato bushy stunt virus (TBSV) with Andy Jackson. In December 1994, Scholthof joined the faculty of the Department of Plant Pathology and Microbiology at Texas A&M University and was promoted to associate professor with tenure in 2000 and to professor in 2005. During sabbatical leaves, he worked as a visiting professor at Harvard Medical School in 2002 and 2003 and at The Boyce Thompson Institute-Cornell University in 2009.
Scholthof had very successful doctoral and post-doctoral experiences. Findings he reported as a graduate student remain highly cited because they involved the discovery of a new regulatory mechanism in eukaryotes that permits translation of polycistronic mRNAs. At the University of California-Berkeley, he continued to make important contributions using TBSV as a model system to study plant virus movement. For instance, Scholthof showed that the capsid protein is not necessary for TBSV to systemically invade some plant hosts. While at Texas A&M University he used this property to develop a TBSV-based gene-vector system that has since been used for groundbreaking research worldwide. Current industry-supported efforts aim to refine and expand the utility of TBSV components in biotechnology.
Much of Scholthof’s work focuses on how TBSV interacts with its hosts to establish systemic invasion and induce symptoms. Foremost, he discovered that two TBSV proteins (P19 and P22) expressed from the same mRNA in plants have entirely different host-dependent roles in pathogenesis. Scholthof elegantly demonstrated the nature of the P19 protein as a pathogenicity factor and found that biological properties of P19 relate to its role as a suppressor of RNA silencing to protect TBSV RNA from degradation, by sequestering short-interfering RNAs (siRNAs) during infection. Structural studies by others provided an explanation for Scholthof’s observations regarding the effect of specific mutations on the structural integrity, biological activity, and siRNA capturing ability of P19. Very recently, he revealed some novel host-dependent properties associated with P19 that appear unrelated to siRNA binding. Another set of original observations made by Scholthof is that the function of P19 is controlled by context-dependent “leaky scanning” to yield a dosage of P19 sufficient to sequester high levels of siRNAs, which is necessary for its efficacy as a suppressor of RNA silencing. Because P19 binds siRNAs in a sequence nonspecific manner, it has become a preferred tool of researchers in the elucidation of RNAi pathways in plants, yeast, and Caenorhabditis elegans.
In this context, Scholthof is widely recognized as an effective and enthusiastic collaborator. He is most generous in distributing TBSV and P19 research materials, which has allowed several dozen plant virology, C. elegans, medical, and molecular biology laboratories to perform experiments that would otherwise not have been feasible. Recently, Scholthof’s group exploited P19-defective mutants to successfully activate a prolific antiviral RNA-induced silencing complex (RISC) in plants. The antiviral RISC was isolated and shown to be programmed with TBSV siRNAs, and it specifically cleaved TBSV RNA in vitro in a divalent cation-dependent manner. This was the first such evidence for an antiviral RISC for any organism and represented a major biochemical advance for the discipline of RNA silencing.
An important distinction of Scholthof’s program is that, while many plant virologists strictly use Nicotiana benthamiana or Arabidopsis thaliana as experimental systems, over the years Scholthof has repeatedly demonstrated that findings with these plants cannot necessarily be directly extrapolated to other (crop) species. Scholthof’s philosophy, as he promulgated in a review article in Plant Physiology, is that critical meaningful information must be obtained outside the perimeter of “model” plant systems, not only in studying virus-host interactions but plant-microbe interactions in general.
Scholthof has also developed the molecular tools to investigate a newly emerged virus transmitted by the wheat curl mite. He reported the first biomolecular characterization of Wheat mosaic virus, a pathogen with no obvious similarities to known viruses, that might serve as an example to elucidate the etiology of similar mite-transmitted diseases.
Scholthof is an enthusiastic teacher of graduate courses in plant virology, molecular methods in plant-microbe interactions, theory of research, and virus gene vectors. He is much sought after as a graduate and undergraduate student mentor and serves on numerous student dissertation committees. He also is a founding member of the Texas A&M Intercollegiate Faculty of Virology. Scholthof has a very well-funded research program and an outstanding record of publication in top-ranked peer-reviewed journals, including Proceedings of the National Academy of Sciences, Journal of Virology, Virology, and Molecular-Plant Microbe Interactions.
In 2004, Scholthof was selected to present a prestigious American Society for Virology State-of-the Art Lecture, and in 2007, he received the APS Ruth Allen Award. Scholthof has served as a panel member for National Institutes of Health, National Science Foundation, and USDA. He was an associate editor and senior editor for both Molecular-Plant Microbe Interactions and Phytopathology and is on the editorial boards of Virology and the Journal of Virology. He regularly organizes, cochairs, and speaks at APS symposia and brings his students to present their research at APS meetings. While Scholthof has an exemplary record of service for APS, his most significant and lasting contributions are his original research findings. He has developed an outstanding, innovative program on the host-dependent roles of virus-encoded proteins, RNA silencing-related host defense mechanisms, and newly emerging diseases.