Chaperoning the driver of filovirus egress to a dead end

ABSTRACT

Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic, virulent pathogens that cause sporadic and global outbreaks of severe hemorrhagic fever. Reemergence of these filoviruses remains a global public health threat, highlighting the need for novel countermeasures to control and treat future disease outbreaks. The EBOV VP40 matrix protein drives virion assembly and egress. We recently reported that BAG3 and HSPA/HSP70, two central components of chaperone-assisted selective autophagy (CASA), target VP40 for autophagic sequestration and degradation, thereby inhibiting virus egress and spread. In addition, we found that expression of the EBOV glycoprotein (GP) activates MTORC1, the gateway regulator of autophagy. Notably, pharmacological suppression of MTORC1 signaling by rapamycin activates autophagy and blocks filovirus egress. These findings highlight the MTORC1-CASA axis as a regulator of filovirus egress and suggest new opportunities for antiviral development and intervention.

KEYWORDS:

• BAG3
• chaperone-assisted selective autophagy
• ebola virus
• filovirus
• HSP70
• MTORC1
• VP40

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Funding was provided in part by NIH grants AI138052, AI139392, AI153815, and EY031465 to R.N.H.; and AI154336 and AI151717 to O.S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article; National Institute of Allergy and Infectious Diseases.