Phase separation in viral infections

Liquid–liquid phase separation (LLPS) leads to the spontaneous formation of membraneless organelles (MLOs), which organize the cytoplasm and nucleus into specialized subregions that accelerate biochemical reactions. Many viruses exploit LLPS to facilitate their replications and to evade antiviral immune responses. In-depth understanding of the physical and biochemical basis underlying LLPS in viral infections might guide the development of a novel class of antivirals. Viruses rely on the reprogramming of cellular processes to enable efficient viral replication; this often requires subcompartmentalization within the host cell. Liquid–liquid phase separation (LLPS) has emerged as a fundamental principle to organize and subdivide cellular processes, and plays an important role in viral life cycles. Despite substantial advances in the field, elucidating the exact organization and function of these organelles remains a major challenge. In this review, we summarize the biochemical basis of condensate formation, the role of LLPS during viral infection, and interplay of LLPS with innate immune responses. Finally, we discuss possible strategies and molecules to modulate LLPS during viral infections. Viruses rely on the reprogramming of cellular processes to enable efficient viral replication; this often requires subcompartmentalization within the host cell. Liquid–liquid phase separation (LLPS) has emerged as a fundamental principle to organize and subdivide cellular processes, and plays an important role in viral life cycles. Despite substantial advances in the field, elucidating the exact organization and function of these organelles remains a major challenge. In this review, we summarize the biochemical basis of condensate formation, the role of LLPS during viral infection, and interplay of LLPS with innate immune responses. Finally, we discuss possible strategies and molecules to modulate LLPS during viral infections. a large family of protein chaperones that are activated in response to stressful stimuli in the cellular environment. nuclear or cytoplasmic membraneless structures composed of multivalent viral proteins combined with the host factors and/or oligonucleotides. IBs are typically built to execute specific replication and assembly functions. highly flexible polypeptide chains that do not adopt well-defined structures in solution yet are fully functional. IDPs can adopt different structures, allowing them to interact with several targets; this capability seems to be advantageous in molecular recognition processes. The IDP functionality may also depend on the transition from a disordered to an ordered structure upon binding to their target. polypeptide segments without precise or well-defined structures. IDRs exist as highly dynamic, disordered conformers that can adopt different structures, which is crucial for their functionality. cellular compartments and condensates formed via phase separation. MLOs organize the cytoplasm and nucleus into specialized subregions, enabling synchronized – and even mutually exclusive – biochemical reactions to take place. a physical process by which a solution of macromolecules, such as proteins or nucleic acids, spontaneously separates into two phases, leading to the formation of MLOs. The propensity of this process is influenced by a wide range of factors, such as the concentration of macromolecule(s), pH, temperature, ionic strength, and the presence of metal ions and small molecules. proteins that interact directly with single-stranded or double-stranded RNA. an MLO assembled via phase separation in response to environmental stress such as heat or cold shock, oxidative and osmotic stress, UV radiation, and viral infections. cellular compartments of altered molecular composition with regard to the cytoplasmic environment, enabling efficient viral translation, replication, particle assembly, and immune evasion. Viral factories depend on the co-option, as well as the exclusion, of specific cellular components. They vary widely among viruses in their composition, shape, and dynamics, ranging from double-membrane vesicles, through spherules, to membraneless organelles.