A mutant retroviral receptor restricts virus superinfection interference and productive infection

Meihong Liu,Maribeth V Eiden

doi:10.1186/1742-4690-9-51

Meihong Liu, Maribeth V Eiden

Open Access

https://doi.org/10.1186/1742-4690-9-51

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Abstract

BackgroundBoth cell-free and cell-associated infection routes are important for retroviral dissemination. Regardless of the mechanism, the driving force of retroviral entry is the interaction between the viral envelope and its receptor. To date it remains unclear how decreased affinity of viruses for their receptors affects viral cell-free infection, cell-cell transmission, and spreading kinetics. We have previously characterized a mutant form of the amphotropic murine retrovirus receptor human phosphate transporter 2 (PiT2) wherein the single substitution of a glutamic acid for the lysine residue at position 522 of this receptor is sufficient to render it to function as a gibbon ape leukemia virus (GALV) receptor.ResultsIn this study we analyzed the binding affinity of the mutant receptor PiT2K522E and determined that it has a 1000 fold decreased GALV envelope binding affinity compared to the GALV wild type receptor. The decreased affinity does not restrict the initiation of cell-free GALV infection. The diminished binding affinity does, however, correlate with a decrease in the ability of GALV to spread in cells expressing this mutant receptor.ConclusionsThe reduced ability of GALV to subsequently spread among cells expressing PiT2K522E is likely resulted from reduced cell-cell transmission, the decreased ability of PiT2K522E-expressing cells to establish superinfection interference, and attendant cytopathic affects.

Highlights

Both cell-free and cell-associated infection routes are important for retroviral dissemination
Productive infection by gibbon ape leukemia virus (GALV) is severely restricted in cells expressing PiT2K522E compared to cells expressing PiT1 both PiT1 and PiT2K522E confer susceptibility to GALV vectors, the ability of PiT2K522E to support infection by replication-competent GALV has not been evaluated
Around 4–5% of MDTFPiT1-HA cells exposed to 0.05 ml GALV-GFP were infected 24 h post-exposure, and maximum infection (93%) was reached at 9 days post-exposure

Summary

Introduction

Both cell-free and cell-associated infection routes are important for retroviral dissemination. We have previously characterized a mutant form of the amphotropic murine retrovirus receptor human phosphate transporter 2 (PiT2) wherein the single substitution of a glutamic acid for the lysine residue at position 522 of this receptor is sufficient to render it to function as a gibbon ape leukemia virus (GALV) receptor. Both cell-free and cell-associated infections are important for retroviral dissemination. Cell-free enveloped viruses bind to specific receptors on the target cell surface They penetrate the host cells by either direct fusion of viral and cellular lipid membranes or via an endocytotic pathway. Several adhesion molecules are recruited to participate at the cell contact site to form a virological synapse and filopodial bridges [5,6,7]

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