Inferring Protein Function in an Emerging Virus: Detection of the Nucleoprotein in Tilapia Lake Virus
Reem Abu Rass, Talia Kustin, Rachel Zamostiano, Nechama Smorodinsky, Daniella Ben Meir, Daniel Feder, Nischay Mishra, W. Ian Lipkin, Avi Eldar, Marcelo Ehrlich, Adi Stern, Eran Bacharach
Abstract
Tilapia is an important source of dietary protein, especially in developing countries. Massive losses of tilapia were identified worldwide, risking the food security of millions of people. Tilapia lake virus (TiLV) is an emerging pathogen responsible for these disease outbreaks. TiLV's genome encodes 10 major proteins, 9 of which show no homology to other known viral or cellular proteins, hindering functionality assessment of these proteins. Here, we describe a novel bioinformatics approach to infer the functionality of TiLV proteins, which predicted Protein 4 as the nucleoprotein, a factor essential for viral RNA replication. We provided experimental support for this prediction by applying multiple molecular, biochemical, and imaging approaches. Overall, we illustrate a strategy for functional analyses in viral discovery. The strategy is important in light of the expected discovery of many unknown viruses and the zoonotic potential of such pathogens.