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Epidemiology of peste des petits ruminants virus in Ethiopia and molecular studies on virulence

Gopilo, Abraham. Epidemiology of peste des petits ruminants virus in Ethiopia and molecular studies on virulence. PhD, Institut National Polytechnique de Toulouse, 2005

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Official URL: http://ethesis.inp-toulouse.fr/archive/00000226/

Abstract

Peste des petits ruminants (PPR) is an acute and highly contagious viral disease of small ruminants, which is characterised by high fever, ocular and nasal discharge, pneumonia, necrosis and ulceration of the mucuous membrane and inflammation of the gastro-intestinal tract leading to severe diarrhoea and high mortality. In Africa, goats are severely affected while sheep undergo a mild form or rarely suffer clinical disease. PPR is one of the most important economical diseases in Ethiopia. Clinical PPR is confirmed in Ethiopian goats, however, its circulation in other animals has never been described. In the present work, we showed that the antibody seroprevalence in camel, cattle, goat and sheep confirmed natural transmission in these animals without clinical disease. The apparent absence of pathogenicity in these animals may have been due to host resistance or loss of virulence of the virus strain. We have further investigated the latter point by in vitro studies on PPRV comparing strains from Ethiopia and other countries with the vaccine strain which has been attenuated after several cell culture passages. In a first approach, virulence of PPRV was monitored in cell culture system and the use of virus specific monoclonal antibodies enabled to detect differences in virulence between PPRV and RPV. Vero (primate origin) and 293T (human) cell lines supported virus replication permitting the in vitro growth of both PPRV and RPV. In contrast to RPV, B95a (marmoset B) cells infected with PPRV were non permissive. The capability of cells to support active virus replication, which may result in intercellular spread and induce damages in infected cells, has implications on the pathogenesis and epidemiology. Cellular receptors are major determinants of host range and tissue tropism of a virus. The difference in infectivity of PPRV and RPV may have depended on the H protein epitopes and their cellular receptors. Therefore, we decided to compare the amino acid epitope of H protein of PPRV with that of other morbilliviruses. As part of our investigation of virulence factors, we have sequenced and compared genome and antigenome promoters of a vaccine strain with field strains of PPRV. The promoters contain the polymerase binding sites to initiate and generate the positive-strand replication and transcription of mRNAs. Nucleotide base change differences between vaccine strain and field strains would provide molecular basis for attenuation. Alignment of the genome promoter sequences revealed seven nucleotide mutations at certain positions. Our finding on nucleotide mutation on PPRV are in agreement with the nucleotide changes in rinderpest virus and other morbillivirus promoter regions between vaccine strain and wild type virus. Certain mutations were specific to PPRV. The promoter sequences were clustered around the geographic origin of the viruses and were lineage specific. Phylogenetic analysis of PPRV promoters was used for PPR phylogeograhy, and for comparison with other paramyxoviruses. The thesis is divided in 6 chapters. The first chapter deals with the natural history of PPR including the virus, the genome, epidemiology, transmission, clinical signs, immunology, diagnosis, control and its economic cost in the low income subsistence farming systems in sub-Saharan Africa. The second chapter is about comparative biology of PPRV with regard to other groups of morbillivirus genus in the Paramyxoviridae family. The third chapter deals with field study and observations on epidemiology of PPR in Ethiopia. In chapter four, PPRV virulence was monitored in cell culture system and comparison of H protein epitopes. In chapter five, sequence analysis of genome and antigenome promoters of PPRV was described In chapter six, general discussion and recommendations were forwarded.

Item Type:PhD Thesis
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Institution: Université de Toulouse > Institut National Polytechnique de Toulouse - INPT
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Research Director:
Picavet, Pierre Dominique
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