tetano
Editor, Senior Moderator
Cell Death Differ. 2011 Dec 2. doi: 10.1038/cdd.2011.178. [Epub ahead of print]
Granzyme K inhibits replication of influenza virus through cleaving the nuclear transport complex importin α1/β dimer of infected host cells.
Zhong C, Li C, Wang X, Toyoda T, Gao G, Fan Z.
Source
CAS Key Laboratory of Infection and Immunity and Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Abstract
The influenza A virus is a causative agent of influenza, which infects human cells and uses host factors to accomplish viral genome replication as part of its life cycle. The nucleoprotein (NP) and PB2 of the influenza virus associate with importin α1 to gain access to the host nucleus through a ternary import complex. Killer cell-mediated cytotoxicity is the primary mechanism of eliminating the influenza virus. Here, we showed that lymphokine-activated killer cells participated in the elimination of the influenza virus. Granzyme (Gzm) K inhibition elevated viral replication in vitro and aggravated viral infection in vivo. We identified that importin α1 and its transport partner protein importin β are physiological substrates of GzmK. Proteolysis of these two substrates wrecked their association to generate the importin α1/β dimer and disrupted transportation of viral NP to the nucleus, leading to inhibition of influenza virus replication.Cell Death and Differentiation advance online publication, 2 December 2011; doi:10.1038/cdd.2011.178.
PMID:
22139131
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22139131
Granzyme K inhibits replication of influenza virus through cleaving the nuclear transport complex importin α1/β dimer of infected host cells.
Zhong C, Li C, Wang X, Toyoda T, Gao G, Fan Z.
Source
CAS Key Laboratory of Infection and Immunity and Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Abstract
The influenza A virus is a causative agent of influenza, which infects human cells and uses host factors to accomplish viral genome replication as part of its life cycle. The nucleoprotein (NP) and PB2 of the influenza virus associate with importin α1 to gain access to the host nucleus through a ternary import complex. Killer cell-mediated cytotoxicity is the primary mechanism of eliminating the influenza virus. Here, we showed that lymphokine-activated killer cells participated in the elimination of the influenza virus. Granzyme (Gzm) K inhibition elevated viral replication in vitro and aggravated viral infection in vivo. We identified that importin α1 and its transport partner protein importin β are physiological substrates of GzmK. Proteolysis of these two substrates wrecked their association to generate the importin α1/β dimer and disrupted transportation of viral NP to the nucleus, leading to inhibition of influenza virus replication.Cell Death and Differentiation advance online publication, 2 December 2011; doi:10.1038/cdd.2011.178.
PMID:
22139131
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22139131