The Influence of Envelope C-Terminus Amino Acid Composition on the Ratio of Cell-Free to Cell-Cell Transmission for Bovine Foamy Virus

Foamy viruses (FVs) have extensive cell tropism in vitro, special replication features, and no clinical pathogenicity in naturally or experimentally infected animals, which distinguish them from orthoretroviruses. Among FVs, bovine foamy virus (BFV) has undetectable or extremely low levels of cell-f...

Full description

Bibliographic Details
Main Authors: Suzhen Zhang, Xiaojuan Liu, Zhibin Liang, Tiejun Bing, Wentao Qiao, Juan Tan
Format: Article
Language:English
Published: MDPI AG 2019-01-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/11/2/130
_version_ 1819060032256344064
author Suzhen Zhang
Xiaojuan Liu
Zhibin Liang
Tiejun Bing
Wentao Qiao
Juan Tan
author_facet Suzhen Zhang
Xiaojuan Liu
Zhibin Liang
Tiejun Bing
Wentao Qiao
Juan Tan
author_sort Suzhen Zhang
collection DOAJ
description Foamy viruses (FVs) have extensive cell tropism in vitro, special replication features, and no clinical pathogenicity in naturally or experimentally infected animals, which distinguish them from orthoretroviruses. Among FVs, bovine foamy virus (BFV) has undetectable or extremely low levels of cell-free transmission in the supernatants of infected cells and mainly spreads by cell-to-cell transmission, which deters its use as a gene transfer vector. Here, using an in vitro virus evolution system, we successfully isolated high-titer cell-free BFV strains from the original cell-to-cell transmissible BFV3026 strain and further constructed an infectious cell-free BFV clone called pBS-BFV-Z1. Following sequence alignment with a cell-associated clone pBS-BFV-B, we identified a number of changes in the genome of pBS-BFV-Z1. Extensive mutagenesis analysis revealed that the C-terminus of envelope protein, especially the K898 residue, controls BFV cell-free transmission by enhancing cell-free virus entry but not the virus release capacity. Taken together, our data show the genetic determinants that regulate cell-to-cell and cell-free transmission of BFV.
first_indexed 2024-12-21T14:20:32Z
format Article
id doaj.art-a9bb881e6a55418d88bde97468084403
institution Directory Open Access Journal
issn 1999-4915
language English
last_indexed 2024-12-21T14:20:32Z
publishDate 2019-01-01
publisher MDPI AG
record_format Article
series Viruses
spelling doaj.art-a9bb881e6a55418d88bde974680844032022-12-21T19:00:48ZengMDPI AGViruses1999-49152019-01-0111213010.3390/v11020130v11020130The Influence of Envelope C-Terminus Amino Acid Composition on the Ratio of Cell-Free to Cell-Cell Transmission for Bovine Foamy VirusSuzhen Zhang0Xiaojuan Liu1Zhibin Liang2Tiejun Bing3Wentao Qiao4Juan Tan5Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, ChinaKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, ChinaKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, ChinaKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, ChinaKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, ChinaKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, ChinaFoamy viruses (FVs) have extensive cell tropism in vitro, special replication features, and no clinical pathogenicity in naturally or experimentally infected animals, which distinguish them from orthoretroviruses. Among FVs, bovine foamy virus (BFV) has undetectable or extremely low levels of cell-free transmission in the supernatants of infected cells and mainly spreads by cell-to-cell transmission, which deters its use as a gene transfer vector. Here, using an in vitro virus evolution system, we successfully isolated high-titer cell-free BFV strains from the original cell-to-cell transmissible BFV3026 strain and further constructed an infectious cell-free BFV clone called pBS-BFV-Z1. Following sequence alignment with a cell-associated clone pBS-BFV-B, we identified a number of changes in the genome of pBS-BFV-Z1. Extensive mutagenesis analysis revealed that the C-terminus of envelope protein, especially the K898 residue, controls BFV cell-free transmission by enhancing cell-free virus entry but not the virus release capacity. Taken together, our data show the genetic determinants that regulate cell-to-cell and cell-free transmission of BFV.https://www.mdpi.com/1999-4915/11/2/130bovine foamy virusinfectious cloneparticle releasecell-free transmission
spellingShingle Suzhen Zhang
Xiaojuan Liu
Zhibin Liang
Tiejun Bing
Wentao Qiao
Juan Tan
The Influence of Envelope C-Terminus Amino Acid Composition on the Ratio of Cell-Free to Cell-Cell Transmission for Bovine Foamy Virus
Viruses
bovine foamy virus
infectious clone
particle release
cell-free transmission
title The Influence of Envelope C-Terminus Amino Acid Composition on the Ratio of Cell-Free to Cell-Cell Transmission for Bovine Foamy Virus
title_full The Influence of Envelope C-Terminus Amino Acid Composition on the Ratio of Cell-Free to Cell-Cell Transmission for Bovine Foamy Virus
title_fullStr The Influence of Envelope C-Terminus Amino Acid Composition on the Ratio of Cell-Free to Cell-Cell Transmission for Bovine Foamy Virus
title_full_unstemmed The Influence of Envelope C-Terminus Amino Acid Composition on the Ratio of Cell-Free to Cell-Cell Transmission for Bovine Foamy Virus
title_short The Influence of Envelope C-Terminus Amino Acid Composition on the Ratio of Cell-Free to Cell-Cell Transmission for Bovine Foamy Virus
title_sort influence of envelope c terminus amino acid composition on the ratio of cell free to cell cell transmission for bovine foamy virus
topic bovine foamy virus
infectious clone
particle release
cell-free transmission
url https://www.mdpi.com/1999-4915/11/2/130
work_keys_str_mv AT suzhenzhang theinfluenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT xiaojuanliu theinfluenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT zhibinliang theinfluenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT tiejunbing theinfluenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT wentaoqiao theinfluenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT juantan theinfluenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT suzhenzhang influenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT xiaojuanliu influenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT zhibinliang influenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT tiejunbing influenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT wentaoqiao influenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus
AT juantan influenceofenvelopecterminusaminoacidcompositionontheratioofcellfreetocellcelltransmissionforbovinefoamyvirus