TY - JOUR
AU - Kreutzberger, Alex J.B.
AU - Sanyal, Anwesha
AU - Saminathan, Anand
AU - Bloyet, Louis Marie
AU - Stumpf, Spencer
AU - Liu, Zhuoming
AU - Ojha, Ravi
AU - Patjas, Markku T.
AU - Geneid, Ahmed
AU - Scanavachi, Gustavo
AU - Doyle, Catherine A.
AU - Somerville, Elliott
AU - da Cunha Correia, Ricardo Bango
AU - Caprio, Giuseppe Di
AU - Toppila-Salmi, Sanna
AU - Mäkitie, Antti
AU - Kiessling, Volker
AU - Vapalahti, Olli
AU - Whelan, Sean P.J.
AU - Balistreri, Giuseppe
AU - Kirchhausen, Tom
PY - 2022
DA - September
TI - SARS-CoV-2 requires acidic pH to infect cells
JO - PNAS
VL - 119
IS - 38
DO - https://doi.org/10.1073/pnas.2209514119
AB - 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.
PB - National Academy of Sciences
UR - https://strathprints.strath.ac.uk/85441/
KW - Coronavirus (COVID-19)
ER