Sustained autophagy contributes to measles virus infectivity

Area of Science:

• Cell Biology
• Virology
• Immunology

Background:

• Autophagy is a cellular defense against pathogens, but microbes can evade or exploit it.
• Measles virus (MeV) interaction with autophagy is complex, with implications for infection control and viral persistence.

Purpose of the Study:

• To elucidate the distinct molecular pathways and timing of autophagy induction by measles virus in permissive cells.
• To understand how measles virus exploits autophagy for its own benefit, including viral replication and cell survival.

Main Methods:

• Investigated autophagy signaling in measles virus-infected cells using specific viral strains and cellular receptors.
• Utilized techniques to track autophagy flux, viral protein degradation, and cell-cell fusion (syncytia) formation.
• Differentiated between early and late autophagy pathways induced by distinct viral components and infection stages.

Main Results:

• Attenuated MeV induces an early, transient autophagy wave via CD46 and GOPC.
• Viral replication and protein C initiate a second, sustained autophagy signaling.
• Cell-cell fusion and syncytia formation lead to a sustained autophagy flux, independent of protein C.
• Measles virus proteins escape autophagic degradation, and the virus exploits sustained autophagy to limit host cell death and promote viral particle production.
• Virulent MeV strains bypass the early pathway but utilize the late, sustained autophagy.

Conclusions:

• Measles virus employs distinct, sequential molecular pathways to induce and exploit sustained autophagy.
• This virus-induced autophagy benefits measles virus by enhancing its replication and survival, while evading degradation.
• Understanding these pathways offers insights into measles pathogenesis and potential therapeutic targets.