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Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting
Published on: March 1, 2019
A pathogenic picornavirus acquires an envelope by hijacking cellular membranes
Zongdi Feng1, Lucinda Hensley, Kevin L McKnight
1Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7292, USA.
Nature
|April 2, 2013
Summary
Hepatitis A virus (HAV) cloaks itself in host cell membranes, creating enveloped HAV (eHAV) particles. This membrane shielding protects the virus from antibody neutralization, impacting its transmission and immune evasion strategies.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Animal viruses are classified by envelope presence, affecting stability and transmission.
- Picornaviridae, a family of non-enveloped RNA viruses, includes Hepatitis A virus (HAV).
- HAV causes enterically transmitted hepatitis, infecting the liver stealthily.
Purpose of the Study:
- To investigate the mechanism behind HAV's ability to evade antibody neutralization.
- To understand how HAV is protected from immune responses despite being classified as non-enveloped.
- To explore the implications of HAV's egress mechanism on viral spread and vaccine efficacy.
Main Methods:
- Characterization of HAV particles released from infected cells.
- Analysis of eHAV infectivity, stability, and presence in human blood.
- Investigation of eHAV biogenesis using host protein inhibitors (VPS4B, ALIX).
Main Results:
- HAV releases enveloped virions (eHAV) cloaked in host-derived membranes.
- eHAV are infectious, chloroform-sensitive, and found in infected human blood.
- eHAV biogenesis depends on ESCRT machinery proteins VPS4B and ALIX.
- eHAV evade antibody neutralization but are susceptible to anti-capsid antibodies.
Conclusions:
- HAV utilizes host membranes for viral egress, blurring the enveloped/non-enveloped virus distinction.
- Membrane cloaking facilitates immune evasion and potentially viral spread within the liver.
- Understanding eHAV formation offers insights into viral pathogenesis and post-exposure prophylaxis strategies.
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