Journal Article

Reduced cellular binding affinity has profoundly different impacts on the spread of distinct poxviruses

Bartee, Eric, Bartee, Mee Y., Flores, Erica B.

2020

Overview

Poxviruses are large enveloped viruses that replicate exclusively in the cytoplasm. Like all viruses, their replication cycle begins with virion adsorption to the cell surface. Unlike most other viral families, however, no unique poxviral receptor has ever been identified. In the absence of a unique receptor, poxviruses are instead thought to adhere to the cell surface primarily through electrostatic interactions between the positively charged viral envelope proteins and the negatively charged sulfate groups on cellular glycosaminoglycans (GAGs). While these negatively charged GAGs are an integral part of all eukaryotic membranes, their specific expression and sulfation patterns differ between cell types. Critically, while poxviral binding has been extensively studied using virally centered genetic strategies, the impact of cell-intrinsic changes to GAG charge has never been examined. Here we show that loss of heparin sulfation, accomplished by deleting the enzyme N-Deacetylase and N-Sulfotransferase-1 (NDST1) which is essential for GAG sulfation, significantly reduces the binding affinity of both vaccinia and myxoma viruses to the cell surface. Strikingly, however, while this lowered binding affinity inhibits the subsequent spread of myxoma virus, it actually enhances the overall spread of vaccinia by generating more diffuse regions of infection. These data indicate that cell-intrinsic GAG sulfation plays a major role in poxviral infection, however, this role varies significantly between different members of the poxviridae.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Affinity / Animals / Anticoagulants / Binding / Biology and Life Sciences / Cell adhesion & migration / Cell Line / Cell surface / Cellulose / Chondroitin sulfate / Cloning / CRISPR / Cytoplasm / Electrostatic properties / Enzymes / Experiments / Flow cytometry / Gag protein / Glycosaminoglycans / Health sciences / Heparin / Heparin - metabolism / Infections / Internal medicine / Intracellular Space - metabolism / Medicine / Medicine and Health Sciences / Mice / Myxoma / N-Deacetylase / N-sulfotransferase / Physical Sciences / Poxviridae - metabolism / Poxviridae - physiology / Protein expression / Proteins / Receptors / Sulfates / Sulfation / Sulfotransferase / Sulfotransferases - deficiency / Vaccinia / Viral infections / Virions / Virus Replication / Viruses