Globoside and the mucosal pH mediate parvovirus B19 entry through the epithelial barrier

Area of Science:

• Virology
• Cell Biology
• Respiratory Medicine

Background:

• Parvovirus B19 (B19V) transmission occurs via the respiratory route, but the precise mechanism is unclear.
• B19V typically infects erythroid progenitor cells using a specific receptor.
• Under acidic conditions, B19V alters its receptor preference to globoside, which is more widely expressed.

Purpose of the Study:

• To investigate the mechanism of Parvovirus B19 (B19V) transmission through the respiratory tract.
• To determine the role of globoside and acidic pH in B19V entry into airway epithelial cells.
• To identify host cell factors involved in B19V transcytosis.

Main Methods:

• Utilized polarized MDCK II cells and human airway epithelial cell (hAEC) cultures as in vitro models.
• Assessed B19V attachment and transcytosis under varying pH conditions (acidic vs. neutral).
• Examined B19V interaction with globoside-deficient cells and investigated the endocytic pathway involved.

Main Results:

• Globoside expression was confirmed in polarized epithelial cells.
• B19V attachment and transcytosis were observed under acidic conditions, mimicking the nasal mucosa, but not at neutral pH.
• Virus entry was blocked in globoside knockout cells, confirming the necessity of globoside and acidic pH for transcellular transport.
• B19V uptake involved the VP2 protein via a clathrin-independent, cholesterol- and dynamin-dependent pathway.

Conclusions:

• The study elucidates a novel mechanism for B19V respiratory transmission involving pH-dependent globoside binding.
• Acidic conditions in the nasal mucosa facilitate B19V entry by enabling interaction with globoside.
• This research identifies specific host factors and pathways that contribute to B19V's ability to breach the epithelial barrier.