Membraneless organelles restructured and built by pandemic viruses: HIV-1 and SARS-CoV-2

Abstract

Viruses hijack host functions to invade their target cells and spread to new cells. Specifically, viruses learned to usurp liquid‒liquid phase separation (LLPS), a newly exploited mechanism, used by the cell to concentrate enzymes to accelerate and confine a wide variety of cellular processes. LLPS gives rise to actual membraneless organelles (MLOs), which do not only increase reaction rates but also act as a filter to select molecules to be retained or to be excluded from the liquid droplet. This is exactly what seems to happen with the condensation of SARS-CoV-2 nucleocapsid protein to favor the packaging of intact viral genomes, excluding viral subgenomic or host cellular RNAs. Another older pandemic virus, HIV-1, also takes advantage of LLPS in the host cell during the viral cycle. Recent discoveries highlighted that HIV-1 RNA genome condensates in nuclear MLOs accompanied by specific host and viral proteins, breaking the dogma of retroviruses that limited viral synthesis exclusively to the cytoplasmic compartment. Intriguing fundamental properties of viral/host LLPS remain still unclear. Future studies will contribute to deeply understanding the role of pathogen-induced MLOs in the epidemic invasion of pandemic viruses.

Keywords: HIV-1; LLPS; MLO; SARS-CoV-2.

Figure 1

MLOs induced by HIV-1 and SARS-CoV-2 to replicate. Left: HIV-1 infection prompts the formation of nuclear MLOs enriched with host factors, such as CPSF6 and SC35, and in viral components, such as vRNA, vDNA, capsid, and integrase. Right: SARS-CoV-2 N protein forms condensates in the cytoplasm to recruit exclusively intact vRNA genome against subgenomic vRNAs or host RNAs. Cartoon created with BioRender.com.