RNA virus replication: from plants to humans
We employ plant viruses as easy-to-use model systems to provide basic understanding of how viruses express genes and replicate. Because of similarities in translation and replication strategies across kingdoms, this knowledge may be relevant to major human viruses such as hepatitis A and C viruses, dengue, West Nile, and others. At a more fundamental level, viruses are fascinating as the smallest, minimal replicating entities. They allow detailed understanding of what it takes to replicate, the essential property that defines life.
How cells decode the genetic code
We investigate the plethora of tricks by which viral messenger RNA usurps and controls the host translational machinery (translation factors and ribosomes). We focus on the structures of viral RNA sequences that recruit host translation factors in the absence of the normally required “5’ cap” modification. This research provides a better understanding of protein synthesis mechanisms and how the genetic code in nucleic acids is converted to amino acid sequence in functional proteins. Who cares? Well, this knowledge may allow us to modify viral sequences to regulate gene expression in beneficial ways, which may even contribute to the design of new anticancer drugs (stay tuned).
Sustainable control of crop diseases and pests
Plants. By sequencing many isolates of barley yellow dwarf and cereal yellow dwarf luteoviruses, we strive to improve the knowledge base of plant pathologists and breeders, who work to manage these viruses. BYDV and CYDV are the most widespread and economically important viruses of wheat, barley and oats, worldwide. They are poorly characterized and vary remarkably in sequence. In a recently finished project, we determined complete nucleotide sequences of dozens of BYDV and CYDV isolates. This work revealed much genome recombination and an entirely new virus, which we call Maize yellow dwarf virus.
In collaboration with Carolyn Malmstrom, Michigan State University, we are studying evolution of YDVs by sequencing viral genomes from old herbarium samples.
Aphids. Under the umbrella of the Virus-Insect Interactions Initiative of the Iowa State University Plant Sciences Institute, we have several projects aimed at controlling aphid pests, and understanding causes of honeybee colony collapse.
In collaboration with Prof. Bryony Bonning (Entomology Dept ISU), we are discovering the first viruses known to infect soybean aphid: a major new pest of soybeans in Iowa.
In collaboration with Prof. Bryony Bonning (Entomology Dept ISU) and Amy Toth (Evolution, Ecology and Organismal Biology Dept, ISU):
- Surveying honeybee colonies for viruses. So far, every colony is infected with multiple viruses.
- Investigating the effect of honeybee nutrition and diet on susceptibility to viruses.
Recent Publications (by area)
NOVEL TRANSLATION MECHANISMS
- Miller WA, Shen R, Staplin WR, Kanodia P (2016) Noncoding RNAs of plant viruses and viroids: sponges of host translation and RNA interference machinery. Molec Plant-Microbe Interact (In press).
- Smirnova E, Firth AE, Miller WA, Scheidecker D, Brault V, Reinbold C, Rakotondrafara AM, Chung B Y-W, Ziegler-Graff V (2015) Discovery of a small non-AUG-initiated ORF in poleroviruses and luteoviruses that is required for long-distance movement. PLoS Pathogens 11, e1004868.
- Miller WA, Jackson J, Feng Y (2015) Cis- and trans-regulation of luteovirus gene expression by the 3' end of the viral genome. Virus Research 206, 37-45.
- Das Sharma S, Kraft JJ, Miller WA, Goss DJ (2015) Recruitment of the 40S ribosomal subunit to the 3'-untranslted region (UTR) of a viral mRNA, via the eIF4 complex, facilitates cap-independent translation. J Biol Chem 290, 11268-11281.
- Miras M, Sempere RN, Kraft JK, Miller WA, Aranda MA, Truniger V (2015) Determination of the Secondary Structure of an RNA fragment in Solution: Selective 2`-Hydroxyl Acylation Analyzed by Primer Extension Assay (SHAPE). bio-protocol 5, www.bio-protocol.org/e1386.
- Miras M, Sempere RN, Kraft JJ, Miller WA, Aranda MA, Truniger V. (2014) Interfamilial recombination between viruses led to acquisition of a novel translation enhancing RNA element that extends viral host range. New Phytologist 202, 233-246.
- Simon AE, Miller WA (2013) 3' Cap-independent translation enhancers of plant viruses. Annual Review of Microbiology 67, 21–42.
- Kraft JJ, Treder K, Peterson MS, Miller WA (2013) Cation-dependent folding of 3' cap-independent translation elements facilitates interaction of a 17-nucleotide conserved sequence with eIF4G. Nucleic Acids Research 41, 3398-3413.
- Carrillo-Tripp J, Bonning BC, Miller WA (2015) Challenges associated with research on RNA viruses of insects. Current Opinion in Insect Science 8, 62-68.
- Miller WA, Carrillo-Tripp J, Bonning BC, Dolezal AG, Toth AL (2014) Conclusive evidence of replication of a plant virus in honeybees is lacking. MBio 5, e00985-14.
- Bonning BC, Pal N, Liu S, Wang Z, Sivakumar S, Dixon PM, King GF, Miller WA (2014) Toxin delivery by the coat protein of an aphid-vectored plant virus provides plant resistance to aphids. Nature Biotechnology 32, 102-105.