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Updated: Jun 8, 2025
Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
Infectious parvovirus B19 circulates in the blood coated with active host protease inhibitors
Hyunwook Lee1, Ruben Assaraf2,3, Suriyasri Subramanian4
1The Hormel Institute, University of Minnesota, Austin, MN, USA.
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 (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.
Insights
Parvovirus B19 (B19V) structures reveal host protease inhibitors shield infectious virions. These inhibitors, ITIH4 and serpinA3, bind to the capsid, aiding immune evasion and protease resistance.
Area of Science:
- Virology
- Structural Biology
- Immunology
Background:
- High-resolution structures of parvovirus B19 (B19V) have been limited to non-infectious virus-like particles (VLPs) due to the lack of permissive cell culture systems.
- Understanding the structure of authentic B19V is crucial for comprehending its infectivity and host interactions.
Purpose of the Study:
- To determine the atomic resolution structure of authentic B19V purified from patient blood.
- To identify host-associated proteins bound to the B19V capsid and investigate their functional implications.
Main Methods:
- Purification of authentic B19V from patient blood samples.
- High-resolution cryo-electron microscopy (cryo-EM) to determine the viral structure.
- Mass spectrometry to identify associated host proteins.
Main Results:
- The atomic resolution structure (2.2 Å) of authentic B19V was determined, revealing significant differences from VLPs.
- Two host protease inhibitors, inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and serpinA3, were found bound to the B19V capsid.
- ITIH4 binds to the fivefold axis, and serpinA3 binds to the twofold axis of the capsid.
- The PI-coated virions remain infectious, with PIs dissociating upon target cell interaction prior to viral entry.
Conclusions:
- Infectious B19V virions are shielded by host serum proteins (ITIH4 and serpinA3), which remain active.
- This shielding mechanism likely facilitates immune evasion and resistance to host protease activity.
- The dissociation of PIs before entry suggests a dynamic interaction with target cells.
