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Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread

Although orthopoxviruses (OPXV) are known to encode a majority of the genes required for replication in host cells, genome-wide genetic screens have revealed that several host pathways are indispensable for OPXV infection. Through a haploid genetic screen, we previously identified several host genes...

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Autores principales: Realegeno, Susan, Priyamvada, Lalita, Kumar, Amrita, Blackburn, Jessica B., Hartloge, Claire, Puschnik, Andreas S., Sambhara, Suryaprakash, Olson, Victoria A., Carette, Jan E., Lupashin, Vladimir, Satheshkumar, Panayampalli Subbian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411930/
https://www.ncbi.nlm.nih.gov/pubmed/32629851
http://dx.doi.org/10.3390/v12070707
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author Realegeno, Susan
Priyamvada, Lalita
Kumar, Amrita
Blackburn, Jessica B.
Hartloge, Claire
Puschnik, Andreas S.
Sambhara, Suryaprakash
Olson, Victoria A.
Carette, Jan E.
Lupashin, Vladimir
Satheshkumar, Panayampalli Subbian
author_facet Realegeno, Susan
Priyamvada, Lalita
Kumar, Amrita
Blackburn, Jessica B.
Hartloge, Claire
Puschnik, Andreas S.
Sambhara, Suryaprakash
Olson, Victoria A.
Carette, Jan E.
Lupashin, Vladimir
Satheshkumar, Panayampalli Subbian
author_sort Realegeno, Susan
collection PubMed
description Although orthopoxviruses (OPXV) are known to encode a majority of the genes required for replication in host cells, genome-wide genetic screens have revealed that several host pathways are indispensable for OPXV infection. Through a haploid genetic screen, we previously identified several host genes required for monkeypox virus (MPXV) infection, including the individual genes that form the conserved oligomeric Golgi (COG) complex. The COG complex is an eight-protein (COG1–COG8) vesicle tethering complex important for regulating membrane trafficking, glycosylation enzymes, and maintaining Golgi structure. In this study, we investigated the role of the COG complex in OPXV infection using cell lines with individual COG gene knockout (KO) mutations. COG KO cells infected with MPXV and vaccinia virus (VACV) produced small plaques and a lower virus yield compared to wild type (WT) cells. In cells where the KO phenotype was reversed using a rescue plasmid, the size of virus plaques increased demonstrating a direct link between the decrease in viral spread and the KO of COG genes. KO cells infected with VACV displayed lower levels of viral fusion and entry compared to WT suggesting that the COG complex is important for early events in OPXV infection. Additionally, fewer actin tails were observed in VACV-infected KO cells compared to WT. Since COG complex proteins are required for cellular trafficking of glycosylated membrane proteins, the disruption of this process due to lack of individual COG complex proteins may potentially impair the virus-cell interactions required for viral entry and egress. These data validate that the COG complex previously identified in our genetic screens plays a role in OPXV infection.
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spelling pubmed-74119302020-08-25 Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread Realegeno, Susan Priyamvada, Lalita Kumar, Amrita Blackburn, Jessica B. Hartloge, Claire Puschnik, Andreas S. Sambhara, Suryaprakash Olson, Victoria A. Carette, Jan E. Lupashin, Vladimir Satheshkumar, Panayampalli Subbian Viruses Article Although orthopoxviruses (OPXV) are known to encode a majority of the genes required for replication in host cells, genome-wide genetic screens have revealed that several host pathways are indispensable for OPXV infection. Through a haploid genetic screen, we previously identified several host genes required for monkeypox virus (MPXV) infection, including the individual genes that form the conserved oligomeric Golgi (COG) complex. The COG complex is an eight-protein (COG1–COG8) vesicle tethering complex important for regulating membrane trafficking, glycosylation enzymes, and maintaining Golgi structure. In this study, we investigated the role of the COG complex in OPXV infection using cell lines with individual COG gene knockout (KO) mutations. COG KO cells infected with MPXV and vaccinia virus (VACV) produced small plaques and a lower virus yield compared to wild type (WT) cells. In cells where the KO phenotype was reversed using a rescue plasmid, the size of virus plaques increased demonstrating a direct link between the decrease in viral spread and the KO of COG genes. KO cells infected with VACV displayed lower levels of viral fusion and entry compared to WT suggesting that the COG complex is important for early events in OPXV infection. Additionally, fewer actin tails were observed in VACV-infected KO cells compared to WT. Since COG complex proteins are required for cellular trafficking of glycosylated membrane proteins, the disruption of this process due to lack of individual COG complex proteins may potentially impair the virus-cell interactions required for viral entry and egress. These data validate that the COG complex previously identified in our genetic screens plays a role in OPXV infection. MDPI 2020-06-30 /pmc/articles/PMC7411930/ /pubmed/32629851 http://dx.doi.org/10.3390/v12070707 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Realegeno, Susan
Priyamvada, Lalita
Kumar, Amrita
Blackburn, Jessica B.
Hartloge, Claire
Puschnik, Andreas S.
Sambhara, Suryaprakash
Olson, Victoria A.
Carette, Jan E.
Lupashin, Vladimir
Satheshkumar, Panayampalli Subbian
Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread
title Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread
title_full Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread
title_fullStr Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread
title_full_unstemmed Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread
title_short Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread
title_sort conserved oligomeric golgi (cog) complex proteins facilitate orthopoxvirus entry, fusion and spread
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411930/
https://www.ncbi.nlm.nih.gov/pubmed/32629851
http://dx.doi.org/10.3390/v12070707
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