Novel Type II Transmembrane Serine Proteases, MSPL and TMPRSS13, Proteolytically Activate Membrane Fusion Activity of the Hemagglutinin of Highly Pathogenic Avian Influenza Viruses and Induce Their Multicycle Replication

• DOI: 10.1128/jvi.02605-09
• Publication Date: 2010-03-11T03:50:02Z
• Authors: Yuushi Okumura; Etsuhisa Takahashi; Mihiro Yano; Masanobu Ohuchi; Tomo Daidoji; Takaaki Nakaya; Eva Böttcher; Wolfgang Garten; Hans-Dieter Klenk; Hiroshi Kido
• Keywords: Furin

Host cellular proteases induce influenza virus entry into cells by cleaving the viral surface envelope glycoprotein hemagglutinin (HA). However, details on involved in this event are not fully available. We report here that ubiquitous type II transmembrane serine proteases, MSPL and its splice variant TMPRSS13, novel candidates for processing HA proteins of highly pathogenic avian (HPAI) viruses, apart from previously identified furin proprotein convertases 5 6. HAs all HPAI H5 H7 strains have one two cleavage site motifs, R-X-K/R-R motif with R at position P4 K-K/R-K/T-R K P4. In studies synthetic 14-residue peptides these preferentially cleaved only R-K-K-R presence calcium other motif, whereas TMPRSS13 both types (those R/K-K-K-R motif) efficiently absence calcium. Full-length recombinant K-K-K-R exhibited poor susceptibility to or infected cells, but it was converted mature subunits transfected expressing membrane-fused giant-cell formation. This conversion membrane fusion were suppressed inhibitors TMPRSS13. Furthermore, infection multiplication genetically modified live A/Crow/Kyoto/53/2004 (H5N1) detected MSPL- TMPRSS13-expressing cells.