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Title | Infectious parvovirus B19 circulates in the blood coated with active host protease inhibitors. |
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Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 9543, Year 2024 |
Publish date | Nov 5, 2024 |
Authors | Hyunwook Lee / Ruben Assaraf / Suriyasri Subramanian / Dan Goetschius / Jan Bieri / Nadia M DiNunno / Remo Leisi / Carol M Bator / Susan L Hafenstein / Carlos Ros / |
PubMed Abstract | The lack of a permissive cell culture system has limited high-resolution structures of parvovirus B19 (B19V) to virus-like particles (VLPs). In this study, we present the atomic resolution structure ...The lack of a permissive cell culture system has limited high-resolution structures of parvovirus B19 (B19V) to virus-like particles (VLPs). In this study, we present the atomic resolution structure (2.2 Å) of authentic B19V purified from a patient blood sample. There are significant differences compared to non-infectious VLPs. Most strikingly, two host protease inhibitors (PIs), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and serpinA3, were identified in complex with the capsids in all patient samples tested. The ITIH4 binds specifically to the icosahedral fivefold axis and serpinA3 occupies the twofold axis. The protein-coated virions remain infectious, and the capsid-associated PIs retain activity; however, upon virion interaction with target cells, the PIs dissociate from the capsid prior to viral entry. Our finding of an infectious virion shielded by bound host serum proteins suggests an evolutionarily favored phenomenon to evade immune surveillance and escape host protease activity. |
External links | Nat Commun / PubMed:39500886 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.2 - 3.2 Å |
Structure data | EMDB-45136, PDB-9c27: EMDB-45160, PDB-9c2t: EMDB-45184, PDB-9c4f: EMDB-45191, PDB-9c4n: EMDB-46607, PDB-9d7k: |
Source |
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Keywords | VIRUS / B19 / Virion / Capsid / VIRAL PROTEIN / PROTEIN BINDING |