Giuseppe
Emeritus
Novel type II transmembrane serine proteases, MSPL and TMPRSS13, proteolytically activate membrane fusion activity of hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication. (J Virol., abstract, edited)
[Source: US National Library of Medicine, LINK. EDITED.]
J Virol. 2010 Mar 10. [Epub ahead of print]
Novel type II transmembrane serine proteases, MSPL and TMPRSS13, proteolytically activate membrane fusion activity of hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication.
Okumura Y, Takahashi E, Yano M, Ohuchi M, Daidoji T, Nakaya T, B?ttcher E, GartenW, Klenk HD, Kido H. - Division of Enzyme Chemistry, Institute for Enzyme Research, Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan; Department of Microbiology, Kawasaki Medical School, Kurashiki 701-0192, Japan; International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Japan; Institute f?r Virologie, Philipps Universit?t, Marburg, Germany.
Host cellular proteases induce influenza virus entry into cells by cleaving viral surface envelope glycoprotein, hemagglutinin (HA). However, details are not fully available on the cellular proteases involved in this event. We report here thatu biquitous type II transmembrane serine proteases, MSPL and its splice variant TMPRSS13, are novel candidates of HA processing proteases of highly pathogenic avian influenza (HPAI) viruses, apart from the reported furin and pro-protein convertase 5/6. There are two cleavage site motifs of HAs in all HPAI H5 and H7 virus strains, one with R-X-K/R-R motif with R at position P4 and the other with K-K/R-K/T-R motif with K at position P4. In studies on 14-residues synthetic HPAI virus HA peptides with these cleavage site motifs, furin preferentially cleaved only HA peptide with R-K-K-R motif in the presence of calcium but not the other, whereas MSPL and TMPRSS13 cleaved both HA peptides of R/K-K-K-R motifs efficiently in the absence of calcium. The full-length recombinant HA of HPAI virus with K-K-K-R cleavage motif was poorly susceptible in the absence of MSPL or TMPRSS13 and the presence of furin in the cells, but it was converted to mature HA subunits with membrane-fused giant cell formation in MSPL or TMPRSS13 transfectant cells. This conversion and membrane fusion were suppressed by inhibitors of MSPL and TMPRSS13. Furthermore, the infection and multiplication of genetically modified live HPAI virus A/Crow/Kyoto/53/2004 (H5N1) with K-K-K-R cleavage site motif was only detected in MSPL- and TMPRSS13-expressing cells.
PMID: 20219906 [PubMed - as supplied by publisher]
J Virol. 2010 Mar 10. [Epub ahead of print]
Novel type II transmembrane serine proteases, MSPL and TMPRSS13, proteolytically activate membrane fusion activity of hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication.
Okumura Y, Takahashi E, Yano M, Ohuchi M, Daidoji T, Nakaya T, B?ttcher E, GartenW, Klenk HD, Kido H. - Division of Enzyme Chemistry, Institute for Enzyme Research, Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan; Department of Microbiology, Kawasaki Medical School, Kurashiki 701-0192, Japan; International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Japan; Institute f?r Virologie, Philipps Universit?t, Marburg, Germany.
Host cellular proteases induce influenza virus entry into cells by cleaving viral surface envelope glycoprotein, hemagglutinin (HA). However, details are not fully available on the cellular proteases involved in this event. We report here thatu biquitous type II transmembrane serine proteases, MSPL and its splice variant TMPRSS13, are novel candidates of HA processing proteases of highly pathogenic avian influenza (HPAI) viruses, apart from the reported furin and pro-protein convertase 5/6. There are two cleavage site motifs of HAs in all HPAI H5 and H7 virus strains, one with R-X-K/R-R motif with R at position P4 and the other with K-K/R-K/T-R motif with K at position P4. In studies on 14-residues synthetic HPAI virus HA peptides with these cleavage site motifs, furin preferentially cleaved only HA peptide with R-K-K-R motif in the presence of calcium but not the other, whereas MSPL and TMPRSS13 cleaved both HA peptides of R/K-K-K-R motifs efficiently in the absence of calcium. The full-length recombinant HA of HPAI virus with K-K-K-R cleavage motif was poorly susceptible in the absence of MSPL or TMPRSS13 and the presence of furin in the cells, but it was converted to mature HA subunits with membrane-fused giant cell formation in MSPL or TMPRSS13 transfectant cells. This conversion and membrane fusion were suppressed by inhibitors of MSPL and TMPRSS13. Furthermore, the infection and multiplication of genetically modified live HPAI virus A/Crow/Kyoto/53/2004 (H5N1) with K-K-K-R cleavage site motif was only detected in MSPL- and TMPRSS13-expressing cells.
PMID: 20219906 [PubMed - as supplied by publisher]