Liquid Biomolecular Condensates and Viral Lifecycles: Review and Perspectives

Abstract

Viruses are highly dependent on the host they infect. Their dependence triggers processes of virus–host co-adaptation, enabling viruses to explore host resources whilst escaping immunity. Scientists have tackled viral–host interplay at differing levels of complexity—in individual hosts, organs, tissues and cells—and seminal studies advanced our understanding about viral lifecycles, intra- or inter-species transmission, and means to control infections. Recently, it emerged as important to address the physical properties of the materials in biological systems; membrane-bound organelles are only one of many ways to separate molecules from the cellular milieu. By achieving a type of compartmentalization lacking membranes known as biomolecular condensates, biological systems developed alternative mechanisms of controlling reactions. The identification that many biological condensates display liquid properties led to the proposal that liquid–liquid phase separation (LLPS) drives their formation. The concept of LLPS is a paradigm shift in cellular structure and organization. There is an unprecedented momentum to revisit long-standing questions in virology and to explore novel antiviral strategies. In the first part of this review, we focus on the state-of-the-art about biomolecular condensates. In the second part, we capture what is known about RNA virus-phase biology and discuss future perspectives of this emerging field in virology.

Comprehensive in virio structure probing analysis of the influenza A virus identifies a functional RNA structure involved in replication and segment interactions

“…In the 87rec virus, a pseudoknot structure was not predicted at nucleotide positions 87 – 130 by IPknot. Thus, the secondary structure at this region was predicted by MXfold2 [42]. The probability at nucleotide positions 87 – 130 in the wild type, 87mut, and 87rec viruses was shown in Figure 3A.…”

New Perspectives on the Biogenesis of Viral Inclusion Bodies in Negative-Sense RNA Virus Infections

“…In the last years, the physical properties of cellular molecules as a key factor for cellular organization gained more and more interest [16,17,[22][23][24]. The mechanism and localization of biochemical processes have been for long years attributed solely to membranesurrounded organelles.…”

“…The transition from soluble molecules to condensates (saturation concentration), liquid crystals, or aggregates is strongly regulated by thermodynamical factors like temperature, concentration, valency, and interaction strength between molecules [28,[44][45][46][47]. The interphase of the different phases results intracellularly in the membrane-less boundary of biomolecular condensates that allow penetration by molecules with similar properties, while it excludes molecules with dissimilar features [20,22,43]. In cell biology, LLPS originates from protein:protein, protein:RNA, or RNA:RNA interactions that lead to the remodeling of a soluble phase into a condensated, dense phase.…”

“…It is therefore also likely that filoviral IBs contact the different cellular compartments to enable material exchange, for example, viral and cellular proteins, and RNA, to favor different viral replication steps (transcription and translation, replication, assembly, condensation and transport of nucleocapsids). It remains to be analyzed if the required ATP provided by mitochondria and the necessary translation of viral and cellular proteins in close proximity to IBs might be covered and orchestrated by the mechanisms of liquid-to-solid transitions [22,189,190].…”

“…The emerging investigations of these highly dynamic structures lead also to a paradigm change with respect to viral IB formation and function. Typical features of biomolecular condensates like dynamics, fusion activity, and reversibility are also characteristic for viral IB formation [19][20][21][22].…”