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			PubMed Journals: J Virol

  Source:		PMID: 21325420


    		J Virol. 2011 May;85(9):4122-34. doi:
     		10.1128/JVI.02232-10. Epub 2011 Feb 16.

			Evidence that TMPRSS2 activates the
			severe acute respiratory syndrome coronavirus
			spike protein for membrane fusion and reduces
			viral control by the humoral immune response.

			Glowacka I(1), Bertram S, Müller MA, Allen
			P, Soilleux E, Pfefferle S, Steffen I, Tsegaye
			TS, He Y, Gnirss K, Niemeyer D, Schneider
			H, Drosten C, Pöhlmann S.

			Author Information
			(1) Institute of Virology, Hannover Medical School,
			30625 Hannover, Germany.

			The spike (S) protein of the
			severe acute respiratory syndrome coronavirus (SARS-CoV) can
			be proteolytically activated by cathepsins
			B and L upon viral uptake into target cell
			endosomes. In contrast, it is largely unknown
			whether host cell proteases located in the
			secretory pathway of infected cells and/or
			on the surface of target cells can cleave
			SARS S. We along with others could previously
			show that the type II transmembrane protease
			TMPRSS2 activates the influenza virus hemagglutinin
			and the human metapneumovirus F protein
			by cleavage. Here, we assessed whether SARS
			S is proteolytically processed by TMPRSS2.
			Western blot analysis revealed that SARS
			S was cleaved into several fragments upon
			coexpression of TMPRSS2 (cis-cleavage) and
			upon contact between SARS S-expressing cells
			and TMPRSS2-positive cells (trans-cleavage).
			cis-cleavage resulted in release of SARS
			S fragments into the cellular supernatant
			and in inhibition of antibody-mediated
			neutralization, most likely because SARS
			S fragments function as antibody decoys.
			trans-cleavage activated SARS S on effector
			cells for fusion with target cells and allowed
			efficient SARS S-driven viral entry into
			targets treated with a lysosomotropic agent
			or a cathepsin inhibitor. Finally, ACE2,
			the cellular receptor for SARS-CoV, and
			TMPRSS2 were found to be coexpressed by
			type II pneumocytes, which represent important
			viral target cells, suggesting that SARS
			S is cleaved by TMPRSS2 in the lung of
			SARS-CoV-infected individuals. In summary,
			we show that TMPRSS2 might promote viral
			spread and pathogenesis by diminishing viral
			recognition by neutralizing antibodies and
			by activating SARS S for cell-cell and virus-cell
			fusion.

			DOI: 10.1128/JVI.02232-10 PMCID: PMC3126222
			PMID: 21325420 [Indexed for MEDLINE]

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