<div><p>Viruses explore the potential multifunctional capacity of the proteins encoded in their compact genome to establish infection. P4 of luteoviruses has emerged as one such multifunctional protein.</p><p>Expressed from an open reading frame (ORF) nested within coat protein ORF, it displays diverse subcellular localizations and interactions, reflecting its complex role in virus infection. In this review we explore how P4, constrained by overlapping ORFs, has evolved multiple functional motifs. We analyze these motifs' conservation across different barley yellow dwarf virus (BYDV) species and related poleroviruses. We also discuss how viral proteins cooperate to facilitate movement and localization of the virus throughout infection. We provide insights into potential future research directions and suggest strategies for developing potential antiviral-resistant approaches.</p></div> <div>Small proteins, versatile functions<p>Viruses infect nearly all life forms on Earth, and they usurp host cellular machinery for their genome replication and spread. For a successful invasion of the host cell and directing the cell environment to the advantage of the virus, viral proteins have several functionalities. These proteins interact with, manipulate, and exploit host proteins to facilitate viral genome replication, suppression of antiviral defenses, intra-and intercellular viral movement, and acquisition and transmission by the insect vectors. Given the compact genome size, viral proteins must be multifunctional, and this multifunctionality comes from the protein structure and sequence [1,2]. Thanks to technological advancements in elucidating protein structural dynamics and protein-protein interactions, we are beginning to understand the molecular basis of the ever-expanding functionality and cooperation of viral proteins. For instance, it was thought that virus-encoded movement proteins (MPs) are involved mainly in virus movement, but recent studies indicate that MP functions go beyond virus movement [3]. In this review we discuss these rapidly expanding research directions of protein multifunctionality and cooperativity by taking an example of the MPs of plant viruses, with a focus on the luteovirus-cereal pathosystem.</p></div>Read less <