AI Article Synopsis
- * Research using advanced tracking techniques reveals that an acidic environment (pH 6.2 to 6.8) is essential for the virus to effectively penetrate and release its genetic material into host cells, even after the initial cleavage events.
- * The study highlights the importance of acidic conditions, which are found in places like the nasal cavity, for enhancing SARS-CoV-2 infection, particularly in cells that express TMPRSS2.
Article Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry starts with membrane attachment and ends with spike (S) protein-catalyzed membrane fusion depending on two cleavage steps, namely, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time three-dimensional single-virion tracking, we show that fusion and genome penetration require virion exposure to an acidic milieu of pH 6.2 to 6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2-overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2-expressing cells in the acidic milieu of the nasal cavity.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499588 | PMC |
| http://dx.doi.org/10.1073/pnas.2209514119 | DOI Listing |
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