The autophagy-related protein ATG5 is a central mediator of a non-canonical autophagy pathway hijacked by HIV-1 to weaken the host’s response to infection

ABSTRACT

Understanding how viruses evade innate defenses to efficiently spread in their hosts is crucial in the fight against infections. In our study, we provided new insights on the first step initiating an LC3C (microtubule associated protein 1 light chain 3 gamma)-associated degradative pathway exploited by HIV-1 (human immunodeficiency virus type 1) to overcome the antiviral action of the restriction factor BST2 (bone marrow stromal cell antigen 2)/tetherin. We have uncovered an unsuspected and unconventional function of the autophagy-related protein ATG5 in the recognition and engagement of BST2 molecules trapping viruses at the plasma membrane, and directing them toward this LC3C-associated pathway for degradation. Additionally, we highlighted that HIV-1 uses this LC3C-associated process to attenuate the inflammatory responses triggered by BST2-mediated sensing of viruses.

KEYWORDS:

• ATG5
• LC3C-associated pathway
• restriction factor
• BST2
• HIV-1
• Vpu

List of abbreviations

AIDS	=	acquired immunodeficiency syndrome
ATG5	=	autophagy related 5
ATG12	=	autophagy related 12
ATG14	=	autophagy related 14
BST2/tetherin	=	bone marrow stromal cell antigen 2
FIP200/RB1CC1	=	RB1inducible coiled-coil 1
HIV-1	=	human immunodeficiency virus type 1
MAP1LC3C/LC3C	=	microtubule associated protein 1 light chain 3 gamma
SYK	=	spleen associated tyrosine kinase
pSYK	=	phosphorylated spleen associated tyrosine kinase
Vpu	=	Viral Protein U

Disclosure statement

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

Additional information

Funding

D.J. holds a fellowship from ANRS and then from SIDACTION. This work is funded by ANRS and SIDACTION.