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Heparan Sulfate Is a Cellular Receptor for Enteric Human Adenoviruses

Anandi Rajan1,2,3, Elin Palm1,2, Fredrik Trulsson1,2,4

  • 1Section of Virology, Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden.

Viruses
|March 6, 2021
PubMed

Insights

Human adenovirus (HAdV)-F40 and -F41, common causes of childhood diarrhea, use a unique short fiber to attach to host cells via heparan sulfate (HS) after stomach acid exposure. This interaction is acid-resistant, aiding viral infection.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Human adenovirus (HAdV)-F40 and -F41 cause significant childhood diarrhea and mortality.
  • HAdV infection mechanisms, particularly receptor interactions, are not fully understood.
  • HAdV-F40 and -F41 have distinct long and short fiber proteins, unlike other HAdVs.

Purpose of the Study:

  • Identify the binding partner for the short fiber of enteric HAdVs.
  • Investigate the role of the short fiber in HAdV infection, especially under acidic conditions.
  • Elucidate the receptor usage switch in enteric HAdVs.

Main Methods:

  • Identified heparan sulfate (HS) as the interaction partner for the short fiber.
  • Demonstrated that acidic pH inactivates the long fiber:CAR interaction.
  • Showed that the short fiber:HS interaction is acid-resistant and enhanced by acidic pH.

Main Results:

  • Heparan sulfate (HS) is identified as the receptor for the short fiber of enteric HAdVs.
  • Acidic pH, mimicking stomach conditions, inactivates the long fiber's binding to CAR.
  • The short fiber:HS interaction remains functional and is enhanced at acidic pH, facilitating host cell attachment.

Conclusions:

  • Enteric HAdVs exhibit a switch in receptor usage from CAR to HS upon exposure to acidic pH.
  • The short fiber plays a crucial role in HAdV attachment and infection, particularly in the stomach environment.
  • Findings offer insights for antiviral drug development and HAdV-based vaccine strategies.

Keywords:
capsid proteinsenteric adenovirusfiber knobsheparan sulfateshort fibers

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