tetano
Editor, Senior Moderator
Nat Commun. 2020 Jan 9;11(1):162. doi: 10.1038/s41467-019-13974-w. [h=1]The inducible amphisome isolates viral hemagglutinin and defends against influenza A virus infection.[/h]
Omi J[SUP]1[/SUP], Watanabe-Takahashi M[SUP]1[/SUP], Igai K[SUP]2[/SUP], Shimizu E[SUP]1[/SUP], Tseng CY[SUP]1[/SUP], Miyasaka T[SUP]3[/SUP], Waku T[SUP]4[/SUP], Hama S[SUP]1[/SUP], Nakanishi R[SUP]1[/SUP], Goto Y[SUP]1[/SUP], Nishino Y[SUP]5[/SUP], Miyazawa A[SUP]5[/SUP], Natori Y[SUP]6[/SUP], Yamashita M[SUP]7[/SUP], Nishikawa K[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The emergence of drug-resistant influenza type A viruses (IAVs) necessitates the development of novel anti-IAV agents. Here, we target the IAV hemagglutinin (HA) protein using multivalent peptide library screens and identify PVF-tet, a peptide-based HA inhibitor. PVF-tet inhibits IAV cytopathicity and propagation in cells by binding to newly synthesized HA, rather than to the HA of the parental virus, thus inducing the accumulation of HA within a unique structure, the inducible amphisome, whose production from the autophagosome is accelerated by PVF-tet. The amphisome is also produced in response to IAV infection in the absence of PVF-tet by cells overexpressing ABC transporter subfamily A3, which plays an essential role in the maturation of multivesicular endosomes into the lamellar body, a lipid-sorting organelle. Our results show that the inducible amphisomes can function as a type of organelle-based anti-viral machinery by sequestering HA. PVF-tet efficiently rescues mice from the lethality of IAV infection.
PMID: 31919357 PMCID: PMC6952414 DOI: 10.1038/s41467-019-13974-w
Free PMC Article
Omi J[SUP]1[/SUP], Watanabe-Takahashi M[SUP]1[/SUP], Igai K[SUP]2[/SUP], Shimizu E[SUP]1[/SUP], Tseng CY[SUP]1[/SUP], Miyasaka T[SUP]3[/SUP], Waku T[SUP]4[/SUP], Hama S[SUP]1[/SUP], Nakanishi R[SUP]1[/SUP], Goto Y[SUP]1[/SUP], Nishino Y[SUP]5[/SUP], Miyazawa A[SUP]5[/SUP], Natori Y[SUP]6[/SUP], Yamashita M[SUP]7[/SUP], Nishikawa K[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The emergence of drug-resistant influenza type A viruses (IAVs) necessitates the development of novel anti-IAV agents. Here, we target the IAV hemagglutinin (HA) protein using multivalent peptide library screens and identify PVF-tet, a peptide-based HA inhibitor. PVF-tet inhibits IAV cytopathicity and propagation in cells by binding to newly synthesized HA, rather than to the HA of the parental virus, thus inducing the accumulation of HA within a unique structure, the inducible amphisome, whose production from the autophagosome is accelerated by PVF-tet. The amphisome is also produced in response to IAV infection in the absence of PVF-tet by cells overexpressing ABC transporter subfamily A3, which plays an essential role in the maturation of multivesicular endosomes into the lamellar body, a lipid-sorting organelle. Our results show that the inducible amphisomes can function as a type of organelle-based anti-viral machinery by sequestering HA. PVF-tet efficiently rescues mice from the lethality of IAV infection.
PMID: 31919357 PMCID: PMC6952414 DOI: 10.1038/s41467-019-13974-w
Free PMC Article