Molecular mechanisms and cellular functions of liquid-liquid phase separation during antiviral immune responses

Abstract

Spatiotemporal separation of cellular components is vital to ensure biochemical processes. Membrane-bound organelles such as mitochondria and nuclei play a major role in isolating intracellular components, while membraneless organelles (MLOs) are accumulatively uncovered via liquid-liquid phase separation (LLPS) to mediate cellular spatiotemporal organization. MLOs orchestrate various key cellular processes, including protein localization, supramolecular assembly, gene expression, and signal transduction. During viral infection, LLPS not only participates in viral replication but also contributes to host antiviral immune responses. Therefore, a more comprehensive understanding of the roles of LLPS in virus infection may open up new avenues for treating viral infectious diseases. In this review, we focus on the antiviral defense mechanisms of LLPS in innate immunity and discuss the involvement of LLPS during viral replication and immune evasion escape, as well as the strategy of targeting LLPS to treat viral infectious diseases.

Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation

“…In the context of viral infections, LLPS has been found to play a significant role, particularly in the case of nonretroviral, single-stranded RNA viruses such as Ebola virus, measles virus, Zika virus, and SARS-CoV-2. [129][130][131][132] LLPS involves the separation of a homogenous polymersolvent mixture into two phases, creating polymer-rich droplets within a diluted phase. 133 This mechanism is crucial in the life cycle of viruses, contributing to processes ranging from viral replication to the evasion of host immune defenses.…”

“…133 This mechanism is crucial in the life cycle of viruses, contributing to processes ranging from viral replication to the evasion of host immune defenses. [129][130][131][132] SARS-CoV-2, for instance, leverages various tactics, including the induction of viral condensates through LLPS, to interfere with host gene expression and suppress the antiviral IFN response, which in turn promotes viral replication and dissemination. [129][130][131][132] In relation to the Zika virus, it's understood that the virus can persist in the central nervous system (CNS) indefinitely, 125 even though specific studies on the role of LLPS in this process are lacking.…”

“…[129][130][131][132] SARS-CoV-2, for instance, leverages various tactics, including the induction of viral condensates through LLPS, to interfere with host gene expression and suppress the antiviral IFN response, which in turn promotes viral replication and dissemination. [129][130][131][132] In relation to the Zika virus, it's understood that the virus can persist in the central nervous system (CNS) indefinitely, 125 even though specific studies on the role of LLPS in this process are lacking. The virus is found within small areas characterized by gliosis and immune cell infiltration.…”

Phenotypic Test of Benzo[4,5]imidazo[1,2-c]pyrimidinone-Based Nucleoside and Non-Nucleoside Derivatives against DNA and RNA Viruses, Including Coronaviruses

“…LLPS has been recognized as a new target for antiviral development due to its important role in the viral life cycle [29,30]. LLPS provides the formation of non-membrane organelles, where enrichment in specific biomolecules is achieved to increase the efficiency of biological processes [29,31].…”

“…LLPS has been recognized as a new target for antiviral development due to its important role in the viral life cycle [29,30]. LLPS provides the formation of non-membrane organelles, where enrichment in specific biomolecules is achieved to increase the efficiency of biological processes [29,31]. DNA damage foci, promyelocytic leukemia nuclear bodies (PML nuclear bodies), Cajal bodies, processing bodies (P-bodies), and stress granules are prominent examples of host cell biocondensates.…”