Studentship: Characterisation of genes involved in the replication-efficiency and transmission of Bluetongue virus (BTV) serotypes 26 and 25

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

IAH studentship: The recently identified bluetongue virus serotypes, BTV-25 and BTV-26, have ‘replication defects’ in certain cell culture systems. Indeed it has so far been impossible to culture BTV-25 in either mammalian or insect cells in vitro. Although BTV-26 replicates in mammalian cells it does not infect/replicate effectively in insect cells.
BTV is usually transmitted between animals by Culicoides (biting midges), but it was recently shown that BTV-26 can be transmitted horizontally between vertebrate hosts (goats) without involving a Culicoides vector. We have established a reverse genetics system for BTV, and have used it to generate mono-reassortants containing individual genome segments of BTV-26 in a BTV-1 background. All BTV-26 segments except Seg-2 (encoding outer capsid protein VP2) have been put into BTV-1, confirming in each case that they can replicate in mammalian cells. One of the reassortants, RG27, which has BTV-26 Seg-7 in BTV-1, was unable to replicate in a Culicoides cell line, whereas the others replicated as well as the BTV-1 parent. Seg-7 encodes the outer core protein VP7. Purified BTV core particles have previously been shown to infect KC cells and adult Culicoides in the absence of the outer capsid proteins that are important for mammalian cell attachment. This indicates that VP7 can mediate infection of insect cells.
BTV-25 and 26 (which show ~98% aa identity in VP7) may not depend on Culicoides vectors for transmission, and may have lost their ability to infect adult Culicoides. The infection/lack of infection in insects may be controlled by VP7, but it is uncertain if VP7 also confers an ability to be transmitted horizontally between vertebrate hosts. This may be controlled by the outer-capsid proteins (particularly VP2) that are considered to be primarily responsible for cell attachment in the mammalian host
 
Description The use of reverse genetics has identified four genome segments that restrict the replication of Bluetongue virus type 26 in Culicoides adults or cell line, but do not inhibit replication in vertebrate host cells. These data contribute significantly to our understanding at the molecular level of the interactions between virus and insect.
Exploitation Route to provide further information concerning the distribution and transmission of these viruses by specific species or populations of vector insects in different geographic regions
Sectors Agriculture, Food and Drink

 
Description "Understanding pathogen, livestock, environment interactions involving bluetongue virus" (PALE-Blu)
Amount € 6,300,000 (EUR)
Funding ID 727393-2 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 06/2016 
End 11/2020