A low-passage insect-cell isolate of bluetongue virus uses a macropinocytosis-like entry pathway to infect natural target cells derived from the bovine host.

Katy Moffat,Peter P C Mertens,Terry Jackson,Karin E Darpel,Lyndsay Cooke,Kyriaki Nomikou,Lisa M Stevens

doi:10.1099/jgv.0.001240

Abstract

Bluetongue virus (BTV) causes an economically important disease in domestic and wildlife ruminants and is transmitted by Culicoides biting midges. In ruminants, BTV has a wide cell tropism that includes endothelial cells of vascular and lymphatic vessels as important cell targets for virus replication, and several cell types of the immune system including monocytes, macrophages and dendritic cells. Thus, cell-entry represents a particular challenge for BTV as it infects many different cell types in widely diverse vertebrate and invertebrate hosts. Improved understanding of BTV cell-entry could lead to novel antiviral approaches that can block virus transmission from cell to cell between its invertebrate and vertebrate hosts. Here, we have investigated BTV cell-entry using endothelial cells derived from the natural bovine host (BFA cells) and purified whole virus particles of a low-passage, insect-cell isolate of a virulent strain of BTV-1. Our results show that the main entry pathway for infection of BFA cells is dependent on actin and dynamin, and shares certain characteristics with macropinocytosis. The ability to use a macropinocytosis-like entry route could explain the diverse cell tropism of BTV and contribute to the efficiency of transmission between vertebrate and invertebrate hosts.

Highlights

Arthropod-borne viruses (Arboviruses) are a diverse group of viruses that collectively cause a wide range of important diseases in man, domesticated animals and wildlife [1]
Bluetongue viruses (BTV)-1 infection of Bovine Foetal Aorta Endothelial Foetal (BFA) cells is partially inhibited by inhibitors of dynamin but does not require clathrinmediated endocytosis
To investigate cell-entry, we used a field-isolate of BTV-1 (BTV-1GIB2007) and a bovine foetal aorta endothelial cell line (BFA cells), representing one of the major cell-types targeted by BTV in the mammalian host

Summary

Introduction

Arthropod-borne viruses (Arboviruses) are a diverse group of viruses that collectively cause a wide range of important diseases in man, domesticated animals and wildlife [1]. Arboviruses are transmitted between susceptible vertebrate hosts by arthropods, such as mosquitoes, ticks, fleas, sand flies and Culicoides spp. Bluetongue virus is the type species of the arbovirus genus Orbivirus (within the family Reoviridae). Bluetongue viruses (BTV) are transmitted by their biological vector, Culicoides biting midges, and can cause a severe hemorrhagic disease [bluetongue (BT)], in naïve individuals belonging to certain species of domesticated and wild ruminants. At least 27 serotypes of BTV have been recognized with further additional serotypes proposed [3,4,5,6,7]. In the last two decades BTV has greatly expanded its geographical distribution northwards culminating in 2006 in a BTV-8 strain spreading for the first time across Northern Europe, reaching as far as Scandinavia [8, 9], which has increased concerns over the potential for further significant BT outbreaks in the region

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Results

Conclusion