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Induction of membraneless organelles as a strategy for HIV-1 post-nuclear entry steps 
Sheng Zhou1,2 , Hongyu Deng1,2,3,*
1CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
2University of Chinese Academy of Sciences, Beijing 100049, China
3CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
*Correspondence to:Hongyu Deng , Email:hydeng@moon.ibp.ac.cn
J Mol Cell Biol, Volume 15, Issue 2, February 2023, mjad013,  https://doi.org/10.1093/jmcb/mjad013

As intracellular parasites, viruses must modulate the environment of host cells to facilitate viral genome replication and virion assembly. One strategy is to establish specialized, membrane-associated subcellular structures to concentrate viral and cellular components and mediate viral replication processes. This strategy is utilized by many positive-strand RNA viruses such as coronaviruses, hepatitis C virus, and Zika virus, and they re-organize host endo-membranes to form double-membrane vesicles for viral genome replication (Wolff et al., 2020). A growing number of studies have uncovered another strategy for subcellular organization—generation of membraneless organelles (MLOs), often mediated by liquid–liquid phase separation (LLPS). These MLOs usually contain proteins with multivalent domains or intrinsically disordered regions (IDRs). Weak interactions between multivalent domains and additional interactions between IDRs and nuclear acids are the main driving forces underlying phase separation (Shin and Brangwynne, 2017). For instance, rabies virus, a negative-strand RNA virus, forms MLOs named inclusion bodies for viral replication (Nikolic et al., 2017). UL112-113 proteins of human cytomegalovirus, a double-stranded (ds) DNA virus, undergo LLPS at viral genomes to form replication compartments in the nucleus, which promotes recruitment of the viral DNA polymerase (Caragliano et al., 2022). In the case of virion assembly, it was recently reported that MLOs named cytoplasmic virion assembly compartments are formed during late infection by murine gammaherpesvirus-68, so as to concentrate dozens of viral structural proteins and facilitate efficient assembly. ORF52, an abundant viral tegument protein, possesses LLPS property and plays an essential role in mediating the formation of this type of MLOs (Zhou et al., 2023).