PT  - JOURNAL ARTICLE
AU  - Päivi Ylä-Anttila
AU  - Maria G. Masucci
TI  - Inhibition of selective autophagy by members of the herpesvirus ubiquitin-deconjugase family
AID  - 10.1101/2021.03.30.437649
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.30.437649
4099  - http://biorxiv.org/content/early/2021/03/30/2021.03.30.437649.short
4100  - http://biorxiv.org/content/early/2021/03/30/2021.03.30.437649.full
AB  - Autophagy is an important component of the innate immune response that restricts infection by different types of pathogens. Viruses have developed multiple strategies to avoid autophagy to complete their replication cycle and promote spreading to new hosts. Here we report that the ubiquitin deconjugases encoded in the N-terminal domain of the large tegument proteins of Epstein-Barr virus (EBV), Kaposi Sarcoma herpesvirus (KSHV) and human cytomegalovirus (HCMV), but not herpes simplex virus-1 (HSV-1), regulate selective autophagy by inhibiting the activity of the autophagy receptor SQSTM1/p62. We found that all the homologs bind to and deubiquitinate SQSTM1/p62 but with variable efficiency, which correlates with their capacity to prevent the colocalization of LC3 with SQSTM1/p62 aggregates and promote the accumulation of a model autophagy substrate. The findings highlight important differences in the strategies by which herpesviruses interfere with selective autophagy.Competing Interest StatementThe authors have declared no competing interest.BPLF1BamH1 fragment left open reading frame-1EBVEpstein-Barr virusGFPgreen fluorescent proteinHTTHuntingtinMAP1LC3/LC3microtubule associated protein 1 light chain 3PB1Phox and Bem1 domainPEphosphatidylethanolamineSQSTM1/p62sequestosome 1UBAubiquitin associated domain