Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2
✍ Scribed by Joerg Glende; Christel Schwegmann-Wessels; Marwan Al-Falah; Susanne Pfefferle; Xiuxia Qu; Hongkui Deng; Christian Drosten; Hassan Y. Naim; Georg Herrler
- Book ID
- 113947617
- Publisher
- Virology Journal
- Year
- 2008
- Tongue
- English
- Weight
- 551 KB
- Volume
- 381
- Category
- Article
- ISSN
- 0042-6822
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✦ Synopsis
Cholesterol present in the plasma membrane of target cells has been shown to be important for the infection
by SARS-CoV. We show that cholesterol depletion by treatment with methyl-β-cyclodextrin (mβCD) affects
infection by SARS-CoV to the same extent as infection by vesicular stomatitis virus-based pseudotypes
containing the surface glycoprotein S of SARS-CoV (VSV-ΔG-S). Therefore, the role of cholesterol for SARSCoV
infection can be assigned to the S protein and is unaffected by other coronavirus proteins. There have
been contradictory reports whether or not angiotensin-converting enzyme 2 (ACE2), the cellular receptor for
SARS-CoV, is present in detergent-resistant membrane domains. We found that ACE2 of both Vero E6 and
Caco-2 cells co-purifies with marker proteins of detergent-resistant membranes supporting the notion that
cholesterol-rich microdomains provide a platform facilitating the efficient interaction of the S protein with
the cellular receptor ACE2. To understand the involvement of cholesterol in the initial steps of the viral life
cycle, we applied a cell-based binding assay with cells expressing the S protein and cells containing
angiotensin-converting enzyme 2 (ACE2). Alternatively, we used a soluble S protein as interaction partner.
Depletion of cholesterol from the ACE2-expressing cells reduced the binding of S-expressing cells by 50%
whereas the binding of soluble S proteinwas not affected. This result suggests that optimal infection requires
a multivalent interaction between viral attachment protein and cellular receptors.
✦ Subjects
Cholesterol Entry Binding SARS-CoV Coronavirus Lipid rafts