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A pathogenic picornavirus acquires an envelope by hijacking cellular membranes
Animal viruses are broadly categorized structurally by the presence or absence of an envelope composed of a lipid-bilayer membrane(1), attributes that profoundly affect stability, transmission, and immune recognition. Among those lacking an envelope, the Picornaviridae are a large and diverse family...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631468/ https://www.ncbi.nlm.nih.gov/pubmed/23542590 http://dx.doi.org/10.1038/nature12029 |
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author | Feng, Zongdi Hensley, Lucinda McKnight, Kevin L. Hu, Fengyu Madden, Victoria Ping, LiFang Jeong, Sook-Hyang Walker, Christopher Lanford, Robert E. Lemon, Stanley M. |
author_facet | Feng, Zongdi Hensley, Lucinda McKnight, Kevin L. Hu, Fengyu Madden, Victoria Ping, LiFang Jeong, Sook-Hyang Walker, Christopher Lanford, Robert E. Lemon, Stanley M. |
author_sort | Feng, Zongdi |
collection | PubMed |
description | Animal viruses are broadly categorized structurally by the presence or absence of an envelope composed of a lipid-bilayer membrane(1), attributes that profoundly affect stability, transmission, and immune recognition. Among those lacking an envelope, the Picornaviridae are a large and diverse family of positive-strand RNA viruses that includes hepatitis A virus (HAV), an ancient human pathogen that remains a common cause of enterically-transmitted hepatitis(2–4). HAV infects in a stealth-like manner and replicates efficiently in the liver(5). Virus-specific antibodies appear only after 3–4 weeks of infection, and typically herald its resolution(3,4). Although unexplained mechanistically, both anti-HAV antibody and inactivated whole-virus vaccines prevent disease when administered as late as 2 weeks after exposure(6), when virus replication is well established in the liver(5). Here, we show that HAV released from cells is cloaked in host-derived membranes, thereby protecting the virion from antibody-mediated neutralization. These enveloped viruses (“eHAV”) resemble exosomes(7), small vesicles that are increasingly recognized to play important roles in intercellular communications. They are fully infectious, sensitive to chloroform extraction, and circulate in the blood of infected humans. Their biogenesis is dependent upon host proteins associated with endosomal-sorting complexes required for transport (ESCRT)(8), VPS4B and ALIX. While the hijacking of membranes by HAV facilitates escape from neutralizing antibodies and likely promotes virus spread within the liver, anti-capsid antibodies restrict replication following infection with eHAV, suggesting a possible explanation for post-exposure prophylaxis. Membrane hijacking by HAV blurs the classic distinction between “enveloped” and “nonenveloped” viruses, and has broad implications for mechanisms of viral egress from infected cells as well as host immune responses. |
format | Online Article Text |
id | pubmed-3631468 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-36314682013-10-18 A pathogenic picornavirus acquires an envelope by hijacking cellular membranes Feng, Zongdi Hensley, Lucinda McKnight, Kevin L. Hu, Fengyu Madden, Victoria Ping, LiFang Jeong, Sook-Hyang Walker, Christopher Lanford, Robert E. Lemon, Stanley M. Nature Article Animal viruses are broadly categorized structurally by the presence or absence of an envelope composed of a lipid-bilayer membrane(1), attributes that profoundly affect stability, transmission, and immune recognition. Among those lacking an envelope, the Picornaviridae are a large and diverse family of positive-strand RNA viruses that includes hepatitis A virus (HAV), an ancient human pathogen that remains a common cause of enterically-transmitted hepatitis(2–4). HAV infects in a stealth-like manner and replicates efficiently in the liver(5). Virus-specific antibodies appear only after 3–4 weeks of infection, and typically herald its resolution(3,4). Although unexplained mechanistically, both anti-HAV antibody and inactivated whole-virus vaccines prevent disease when administered as late as 2 weeks after exposure(6), when virus replication is well established in the liver(5). Here, we show that HAV released from cells is cloaked in host-derived membranes, thereby protecting the virion from antibody-mediated neutralization. These enveloped viruses (“eHAV”) resemble exosomes(7), small vesicles that are increasingly recognized to play important roles in intercellular communications. They are fully infectious, sensitive to chloroform extraction, and circulate in the blood of infected humans. Their biogenesis is dependent upon host proteins associated with endosomal-sorting complexes required for transport (ESCRT)(8), VPS4B and ALIX. While the hijacking of membranes by HAV facilitates escape from neutralizing antibodies and likely promotes virus spread within the liver, anti-capsid antibodies restrict replication following infection with eHAV, suggesting a possible explanation for post-exposure prophylaxis. Membrane hijacking by HAV blurs the classic distinction between “enveloped” and “nonenveloped” viruses, and has broad implications for mechanisms of viral egress from infected cells as well as host immune responses. 2013-03-31 2013-04-18 /pmc/articles/PMC3631468/ /pubmed/23542590 http://dx.doi.org/10.1038/nature12029 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Feng, Zongdi Hensley, Lucinda McKnight, Kevin L. Hu, Fengyu Madden, Victoria Ping, LiFang Jeong, Sook-Hyang Walker, Christopher Lanford, Robert E. Lemon, Stanley M. A pathogenic picornavirus acquires an envelope by hijacking cellular membranes |
title | A pathogenic picornavirus acquires an envelope by hijacking cellular membranes |
title_full | A pathogenic picornavirus acquires an envelope by hijacking cellular membranes |
title_fullStr | A pathogenic picornavirus acquires an envelope by hijacking cellular membranes |
title_full_unstemmed | A pathogenic picornavirus acquires an envelope by hijacking cellular membranes |
title_short | A pathogenic picornavirus acquires an envelope by hijacking cellular membranes |
title_sort | pathogenic picornavirus acquires an envelope by hijacking cellular membranes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631468/ https://www.ncbi.nlm.nih.gov/pubmed/23542590 http://dx.doi.org/10.1038/nature12029 |
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