Extended receptor repertoire of an adenovirus associated with human obesity
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Human adenovirus type 36 (HAdV-D36) has been putatively linked to obesity in animals and has been associated with obesity in humans in some but not all studies. Despite extensive epidemiological research there is limited information about its receptor profile. We investigated the receptor portfolio of HAdV-D36 using a combined structural biology and virology approach. The HAdV-D36 fiber knob domain (FK), which mediates the primary attachment of many HAdVs to host cells, has a significantly elongated DG loop that alters known binding interfaces for established adenovirus receptors such as the coxsackie- and adenovirus receptor (CAR) and CD46. Our data suggest that HAdV-D36 attaches to host cells using a versatile receptor pool comprising sialic acid-containing glycans and CAR. Sialic acids are recognized at the same binding site used by other HAdVs of species D such as HAdV-D37. Using glycan microarrays, we demonstrate that HAdV-D36 displays a binding preference for glycans containing a rare sialic acid variant, 4-O,5-N-diacetylneuraminic acid, over the more common 5-N-acetylneuraminic acid. To date, this sialic acid variant has not been detected in humans, although it can be synthesized by various animal species, including a range of domestic and livestock animals. Taken together, our results indicate that HAdV-D36 has evolved to recognize a specialized set of primary attachment receptors that are different from known HAdV types and coincides with a unique host range and pathogenicity profile.
Editor(s)
Heldwein, Ekaterina E
Date Issued
2025-01-30
Date Acceptance
2025-01-07
Citation
PLoS Pathogens, 2025, 21 (1)
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Pathogens
Volume
21
Issue
1
Copyright Statement
© 2025 Liaci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39883726
PII: PPATHOGENS-D-24-02313
Subjects
AD-36
ADIPOSITY
ATTACHMENT
BINDING
CELLULAR RECEPTOR
IMMUNOGENICITY
INFECTOBESITY
Life Sciences & Biomedicine
MEMBRANE COFACTOR PROTEIN
Microbiology
Parasitology
Science & Technology
USES SIALIC-ACID
VACCINE
Virology
Publication Status
Published
Coverage Spatial
United States
Article Number
e1012892
Date Publish Online
2025-01-30