IAH-Funded studentship: Mechanisms of control of host innate immune responses by peste des petits ruminants virus (PPRV)

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

Peste des petits ruminants (PPR) is a contagious viral disease affecting sheep and goats; it is endemic in the Indian sub-continent, the Middle East, and many regions of North Africa and continues to spread, with recent first outbreaks in Tanzania, Uganda, Morocco and China. Infected animals get a sudden fever, with eye and nose discharge, diarrhoea and sometimes pneumonia. Mortality rates are usually around 20%, and the disease has knock-on effects on fertility and production in surviving animals. The virus that causes this disease (PPRV) is a member of the genus Morbillivirus, and is closely related to a number of other common viruses, including measles virus. We have been studying the way this group of viruses blocks host defenses, particularly the production of the anti-viral cytokines known as interferons (IFNs). All of these viruses produce two non-structural proteins, C & V, which are involved in blocking the induction or action of IFNs, but the different viruses have different mechanisms. Our preliminary data show that PPRV differs from other morbilliviruses in two ways; both its V and its C block IFN induction (it is only the C in the other viruses) and yet neither the C nor the V of PPRV are very effective, alone or together. The aims of this project are to investigate how the PPRV V protein blocks IFN induction and whether the unique features of the PPRV proteins are due to specific adaptation to the animals in which the virus causes disease. The student will identify the point in the IFN induction pathway where PPRV acts and identify the host protein with which it interacts using transient expression as well as V-expressing cell lines. Mutant proteins containing parts of PPRV V and parts of the V protein of another virus will be used to identify the functional part of PPRV V. In addition, the ability of the PPRV proteins to block IFN induction In cells derived from different animals will be compared to see if there is any host- specificity of effect.

Publications

10 25 50
 
Description Confirmed the methods by which PPRV inhibits interferon production. Showed that these are multifactorial
Exploitation Route Development of modified PPRV for in vivo studies
Sectors Agriculture, Food and Drink

 
Description Project is ongoing. Findings have been used so far to develop new research ideas.