tetano
Editor, Senior Moderator
J Virol. 2013 Sep 11. [Epub ahead of print]
Influenza A virus proteins NS1 and HA along with M2 are involved in stimulation of autophagy in infected cells.
Zhirnov OP, Klenk HD.
Source
D.I.Ivanovsky Institute of Virology, Moscow 123098, Russia.
Abstract
The NS1 protein of Influenza A virus is known to down-regulate apoptosis early in infection in order to support virus replication (1). We have analyzed here the development of autophagy, another mechanism to protect cells from degradation, as depending on NS1 expression. To this end we have compared autophagy in cells infected with wild type influenza virus and virus lacking the NS1 gene (del NS1). The results show that in WT-infected, but not in delNS1-infected, cells synthesis of the autophagy marker LC3-II, the lipidated form of microtubule light chain associated protein LC3, is stimulated, and that LC3-II accumulates in a perinuclear zone enriched with double layered membrane vesicles characteristic of autophagosomes. Transfection experiments revealed that NS1 expressed alone was unable to up-regulate autophagy, whereas HA and M2 did. Proteolytic cleavage of HA increased autophagy. Taken together these observations indicate that NS1 stimulates autophagy indirectly by up-regulating synthesis of HA and M2. Thus, it appears that NS1, besides down-regulating apoptosis, is involved in up-regulation of autophagy and that it supports by both mechanisms survival of the infected cells.
PMID:
24027311
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24027311
Influenza A virus proteins NS1 and HA along with M2 are involved in stimulation of autophagy in infected cells.
Zhirnov OP, Klenk HD.
Source
D.I.Ivanovsky Institute of Virology, Moscow 123098, Russia.
Abstract
The NS1 protein of Influenza A virus is known to down-regulate apoptosis early in infection in order to support virus replication (1). We have analyzed here the development of autophagy, another mechanism to protect cells from degradation, as depending on NS1 expression. To this end we have compared autophagy in cells infected with wild type influenza virus and virus lacking the NS1 gene (del NS1). The results show that in WT-infected, but not in delNS1-infected, cells synthesis of the autophagy marker LC3-II, the lipidated form of microtubule light chain associated protein LC3, is stimulated, and that LC3-II accumulates in a perinuclear zone enriched with double layered membrane vesicles characteristic of autophagosomes. Transfection experiments revealed that NS1 expressed alone was unable to up-regulate autophagy, whereas HA and M2 did. Proteolytic cleavage of HA increased autophagy. Taken together these observations indicate that NS1 stimulates autophagy indirectly by up-regulating synthesis of HA and M2. Thus, it appears that NS1, besides down-regulating apoptosis, is involved in up-regulation of autophagy and that it supports by both mechanisms survival of the infected cells.
PMID:
24027311
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24027311