SARS-CoV-2 requires acidic pH to infect cells

Area of Science:

• Virology
• Cell Biology
• Biochemistry

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes its spike (S) protein for cell entry, involving membrane attachment and fusion.
• S protein-mediated fusion is dependent on proteolytic cleavage, typically by furin and TMPRSS2, or endosomal cathepsins.

Purpose of the Study:

• To investigate the role of pH in SARS-CoV-2 cell entry and fusion.
• To elucidate the sequential steps of viral fusion and genome penetration under varying pH conditions.

Main Methods:

• Real-time three-dimensional single-virion tracking.
• Analysis of viral fusion and content release in TMPRSS2-overexpressing cells at different pH levels.

Main Results:

• SARS-CoV-2 fusion and genome penetration necessitate exposure to an acidic milieu (pH 6.2–6.8).
• Acidic pH is required for S1-fragment dissociation, fusion, and content release, even when furin and TMPRSS2 cleavages are complete.
• An acidic environment is critical for infection at the cell surface of TMPRSS2-expressing cells and within endosomal compartments.

Conclusions:

• An acidic environment plays a key role in facilitating SARS-CoV-2 cell entry.
• The findings highlight the importance of pH in viral fusion and infection mechanisms, particularly in the nasal cavity and endosomes.