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Clathrin Facilitates the Morphogenesis of Retrovirus Particles

The morphogenesis of retroviral particles is driven by Gag and GagPol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation. In addition, a number of cellular proteins are found in retrovirus particles; some of these are important...

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Autores principales: Zhang, Fengwen, Zang, Trinity, Wilson, Sam J., Johnson, Marc C., Bieniasz, Paul D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128127/
https://www.ncbi.nlm.nih.gov/pubmed/21738476
http://dx.doi.org/10.1371/journal.ppat.1002119
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author Zhang, Fengwen
Zang, Trinity
Wilson, Sam J.
Johnson, Marc C.
Bieniasz, Paul D.
author_facet Zhang, Fengwen
Zang, Trinity
Wilson, Sam J.
Johnson, Marc C.
Bieniasz, Paul D.
author_sort Zhang, Fengwen
collection PubMed
description The morphogenesis of retroviral particles is driven by Gag and GagPol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation. In addition, a number of cellular proteins are found in retrovirus particles; some of these are important for viral replication, but many lack a known functional role. One such protein is clathrin, which is assumed to be passively incorporated into virions due to its abundance at the plasma membrane. We found that clathrin is not only exceptionally abundant in highly purified HIV-1 particles but is recruited with high specificity. In particular, the HIV-1 Pol protein was absolutely required for clathrin incorporation and point mutations in reverse transcriptase or integrase domains of Pol could abolish incorporation. Clathrin was also specifically incorporated into other retrovirus particles, including members of the lentivirus (simian immunodeficiency virus, SIVmac), gammaretrovirus (murine leukemia virus, MLV) and betaretrovirus (Mason-Pfizer monkey virus, M-PMV) genera. However, unlike HIV-1, these other retroviruses recruited clathrin primarily using peptide motifs in their respective Gag proteins that mimicked motifs found in cellular clathrin adaptors. Perturbation of clathrin incorporation into these retroviruses, via mutagenesis of viral proteins, siRNA based clathrin depletion or adaptor protein (AP180) induced clathrin sequestration, had a range of effects on the accuracy of particle morphogenesis. These effects varied according to which retrovirus was examined, and included Gag and/or Pol protein destabilization, inhibition of particle assembly and reduction in virion infectivity. For each retrovirus examined, clathrin incorporation appeared to be important for optimal replication. These data indicate that a number of retroviruses employ clathrin to facilitate the accurate morphogenesis of infectious particles. We propose a model in which clathrin contributes to the spatial organization of Gag and Pol proteins, and thereby regulates proteolytic processing of virion components during particle assembly.
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spelling pubmed-31281272011-07-07 Clathrin Facilitates the Morphogenesis of Retrovirus Particles Zhang, Fengwen Zang, Trinity Wilson, Sam J. Johnson, Marc C. Bieniasz, Paul D. PLoS Pathog Research Article The morphogenesis of retroviral particles is driven by Gag and GagPol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation. In addition, a number of cellular proteins are found in retrovirus particles; some of these are important for viral replication, but many lack a known functional role. One such protein is clathrin, which is assumed to be passively incorporated into virions due to its abundance at the plasma membrane. We found that clathrin is not only exceptionally abundant in highly purified HIV-1 particles but is recruited with high specificity. In particular, the HIV-1 Pol protein was absolutely required for clathrin incorporation and point mutations in reverse transcriptase or integrase domains of Pol could abolish incorporation. Clathrin was also specifically incorporated into other retrovirus particles, including members of the lentivirus (simian immunodeficiency virus, SIVmac), gammaretrovirus (murine leukemia virus, MLV) and betaretrovirus (Mason-Pfizer monkey virus, M-PMV) genera. However, unlike HIV-1, these other retroviruses recruited clathrin primarily using peptide motifs in their respective Gag proteins that mimicked motifs found in cellular clathrin adaptors. Perturbation of clathrin incorporation into these retroviruses, via mutagenesis of viral proteins, siRNA based clathrin depletion or adaptor protein (AP180) induced clathrin sequestration, had a range of effects on the accuracy of particle morphogenesis. These effects varied according to which retrovirus was examined, and included Gag and/or Pol protein destabilization, inhibition of particle assembly and reduction in virion infectivity. For each retrovirus examined, clathrin incorporation appeared to be important for optimal replication. These data indicate that a number of retroviruses employ clathrin to facilitate the accurate morphogenesis of infectious particles. We propose a model in which clathrin contributes to the spatial organization of Gag and Pol proteins, and thereby regulates proteolytic processing of virion components during particle assembly. Public Library of Science 2011-06-30 /pmc/articles/PMC3128127/ /pubmed/21738476 http://dx.doi.org/10.1371/journal.ppat.1002119 Text en Zhang et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Zhang, Fengwen
Zang, Trinity
Wilson, Sam J.
Johnson, Marc C.
Bieniasz, Paul D.
Clathrin Facilitates the Morphogenesis of Retrovirus Particles
title Clathrin Facilitates the Morphogenesis of Retrovirus Particles
title_full Clathrin Facilitates the Morphogenesis of Retrovirus Particles
title_fullStr Clathrin Facilitates the Morphogenesis of Retrovirus Particles
title_full_unstemmed Clathrin Facilitates the Morphogenesis of Retrovirus Particles
title_short Clathrin Facilitates the Morphogenesis of Retrovirus Particles
title_sort clathrin facilitates the morphogenesis of retrovirus particles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128127/
https://www.ncbi.nlm.nih.gov/pubmed/21738476
http://dx.doi.org/10.1371/journal.ppat.1002119
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