Formation and Function of Liquid-Like Viral Factories in Negative-Sense Single-Stranded RNA Virus Infections

Figure 1. Schematic diagram of measles virus (MeV) multiplication cycle. MeV possesses a negative-sense, single-stranded RNA genome of ~15.9 kb. Virus multiplication occurs in the cytoplasm. Following receptor-mediated virion attachment, the viral envelope fuses with host membranes, releasing the ribonucleocapsid (RNP) complex consisting of genome RNA encapsidated by nucleoprotein N into the cytoplasm; this triggers activation of the virion-associated RNA polymerase complex of viral L and P proteins. The RNP constitutes the basic machinery responsible for RNA synthesis, initially for transcription and then for replication. These processes are thought to be associated with the cytoplasmic inclusion body (IB) factories. Viral C protein interacts with P and enhances polymerase processivity; in the absence of C, defective interfering (DI) RNAs are readily formed. IB assembly triggered by MeV infection is mediated by liquid–liquid phase separation (LLPS). MeV N and P proteins are sufficient to form IB structures by LLPS. The viral matrix M protein mediates assembly of progeny enveloped virions that include two viral glycoproteins, the hemagglutinin H attachment protein and the F fusion protein.