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

Suzhen Zhang,Zhibin Liang,Xiaojuan Liu,Wentao Qiao,Juan Tan,Tiejun Bing

doi:10.3390/v11020130

Abstract

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.

Highlights

Foamy viruses (FVs), known as spumaviruses, are a group of Retroviridae with unique features that differentiate them from orthoretroviruses
Unlike most other retroviruses, such as the human immunodeficiency virus (HIV) [12,13,14,15,16], murine leukemia virus (MLV), feline foamy virus (FFV), prototype foamy virus (PFV), and simian foamy virus (SFV), which transmit through both cell-to-cell and cell-free pathways, bovine foamy virus (BFV) infection is tightly cell-associated [17,18]
We identified the viral genes and key amino acids that regulate BFV cell-free transmission

Summary

Introduction

Foamy viruses (FVs), known as spumaviruses, are a group of Retroviridae with unique features that differentiate them from orthoretroviruses. FVs infect humans [1,2] and other mammals, including bovines [3], simians [4], felines [5], and equines [6]. Unlike most other retroviruses, such as the human immunodeficiency virus (HIV) [12,13,14,15,16], murine leukemia virus (MLV), feline foamy virus (FFV), prototype foamy virus (PFV), and simian foamy virus (SFV), which transmit through both cell-to-cell and cell-free pathways, bovine foamy virus (BFV) infection is tightly cell-associated [17,18]

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Conclusion