tetano
Editor, Senior Moderator
Virol Sin. 2018 Oct 16. doi: 10.1007/s12250-018-0058-6. [Epub ahead of print]
[h=1]CypA Regulates AIP4-Mediated M1 Ubiquitination of Influenza A Virus.[/h] Mahesutihan M[SUP]1,[/SUP][SUP]2[/SUP], Zheng W[SUP]1[/SUP], Cui L[SUP]1,[/SUP][SUP]2[/SUP], Li Y[SUP]1[/SUP], Jiao P[SUP]3[/SUP], Yang W[SUP]1,[/SUP][SUP]2[/SUP], Liu W[SUP]4[/SUP], Li J[SUP]1[/SUP], Fan W[SUP]1[/SUP], Yang L[SUP]1[/SUP], Liu W[SUP]5,[/SUP][SUP]6[/SUP], Sun L[SUP]7,[/SUP][SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Cyclophilin A (CypA) is a peptidyl-prolyl cis/trans isomerase that interacts with the matrix protein (M1) of influenza A virus (IAV) and restricts virus replication by regulating the ubiquitin-proteasome-mediated degradation of M1. However, the mechanism by which CypA regulates M1 ubiquitination remains unknown. In this study, we reported that E3 ubiquitin ligase AIP4 promoted K48-linked ubiquitination of M1 at K102 and K104, and accelerated ubiquitin-proteasome-mediated degradation of M1. The recombinant IAV with mutant M1 (K102R/K104R) could not be rescued, suggesting that the ubiquitination of M1 at K102/K104 was essential for IAV replication. Furthermore, CypA inhibited AIP4-mediated M1 ubiquitination by impairing the interaction between AIP4 and M1. More importantly, both the mutations of M1 (K102R/K104R) and CypA inhibited the nuclear export of M1, indicating that CypA regulates the cellular localization of M1 via inhibition of AIP4-mediated M1 ubiquitination at K102 and K104, which results in the reduced replication of IAV. Collectively, our findings reveal a novel ubiquitination-based mechanism by which CypA regulates the replication of IAV.
[h=4]KEYWORDS:[/h] AIP4; Cyclophilin A (CypA); Influenza A virus (IAV); M1; Ubiquitination
PMID: 30328013 DOI: 10.1007/s12250-018-0058-6
[h=1]CypA Regulates AIP4-Mediated M1 Ubiquitination of Influenza A Virus.[/h] Mahesutihan M[SUP]1,[/SUP][SUP]2[/SUP], Zheng W[SUP]1[/SUP], Cui L[SUP]1,[/SUP][SUP]2[/SUP], Li Y[SUP]1[/SUP], Jiao P[SUP]3[/SUP], Yang W[SUP]1,[/SUP][SUP]2[/SUP], Liu W[SUP]4[/SUP], Li J[SUP]1[/SUP], Fan W[SUP]1[/SUP], Yang L[SUP]1[/SUP], Liu W[SUP]5,[/SUP][SUP]6[/SUP], Sun L[SUP]7,[/SUP][SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Cyclophilin A (CypA) is a peptidyl-prolyl cis/trans isomerase that interacts with the matrix protein (M1) of influenza A virus (IAV) and restricts virus replication by regulating the ubiquitin-proteasome-mediated degradation of M1. However, the mechanism by which CypA regulates M1 ubiquitination remains unknown. In this study, we reported that E3 ubiquitin ligase AIP4 promoted K48-linked ubiquitination of M1 at K102 and K104, and accelerated ubiquitin-proteasome-mediated degradation of M1. The recombinant IAV with mutant M1 (K102R/K104R) could not be rescued, suggesting that the ubiquitination of M1 at K102/K104 was essential for IAV replication. Furthermore, CypA inhibited AIP4-mediated M1 ubiquitination by impairing the interaction between AIP4 and M1. More importantly, both the mutations of M1 (K102R/K104R) and CypA inhibited the nuclear export of M1, indicating that CypA regulates the cellular localization of M1 via inhibition of AIP4-mediated M1 ubiquitination at K102 and K104, which results in the reduced replication of IAV. Collectively, our findings reveal a novel ubiquitination-based mechanism by which CypA regulates the replication of IAV.
[h=4]KEYWORDS:[/h] AIP4; Cyclophilin A (CypA); Influenza A virus (IAV); M1; Ubiquitination
PMID: 30328013 DOI: 10.1007/s12250-018-0058-6