Peste des petits ruminants

Abstract

Peste des petits ruminants virus causes a highly infectious disease of small ruminants that is endemic across Africa, the Middle East and large regions of Asia. The virus is considered to be a major obstacle to the development of sustainable agriculture across the developing world and has recently been targeted by the World Organisation for Animal Health (OIE) and the Food and Agriculture Organisation (FAO) for eradication with the aim of global elimination of the disease by 2030. Fundamentally, the vaccines required to successfully achieve this goal are currently available, but the availability of novel vaccine preparations to also fulfill the requisite for differentiation between infected and vaccinated animals (DIVA) may reduce the time taken and the financial costs of serological surveillance in the later stages of any eradication campaign. Here, we overview what is currently known about the virus, with reference to its origin, updated global circulation, molecular evolution, diagnostic tools and vaccines currently available to combat the disease. Further, we comment on recent developments in our knowledge of various recombinant vaccines and on the potential for the development of novel multivalent vaccines for small ruminants.

Keywords: Control and eradication; Country-wise virus circulation; Live attenuated vaccine; Molecular evolution; PPR; Pathogenesis; Potential DIVA and multivalent vaccine; Reverse genetics.

Fig. 1

Un-rooted neighbour-joining tree showing the relationships between different morbiliviruses. The phylogenetic tree was constructed using partial N gene sequences of 230 nucleotides (accession nos. NC_006383, Peste des petits ruminants virus; NC_001498, Measles virus; AB547189, Rinderpest virus; NC_001921, Canine distemper virus; KC802221, Phocine distemper virus; JQ411016, Feline morbillivirus; AY949833, Porpoise morbillivirus; NC_005283, Dolphin morbillivirus; AF200818, Pilot whale morbillivirus) with 1000 bootstrap replicates and Kimura 2-parameter model in MEGA 5.2. The scale bar indicates nucleotide substitutions per site.

Fig. 2

(a) Schematic diagram of Peste des petits ruminants virion structure (adapted from Banyard et al., 2010). The PPRV glycoproteins (F and H) are embedded within the viral envelope. The M protein lines the inner surface of virus envelope. The ribonucleoprotein complex is composed of N, P and L proteins in association with the RNA genome. (b) Electron micrograph of peste des petits ruminants nuclocapsid in the cytoplasm of an infected cell. The viral RNA, completely encapsidated in the viral N protein has a herring-bone like appearance (arrow).

Fig. 3

Schematic representation of Peste des petits ruminants virus genome organisation. The PPRV genome is a non-segmented, single-stranded negative sense RNA molecule. The genome consists of six transcriptional units (encoding the nucleoprotein [N], phosphoprotein [P], matrix protein [M], fusion protein [F], haemagglutinin protein [H] and the large/polymerase [L] protein) that are flanked by a 3′ genome promoter (GP) and a 5′ anti-genome promoter (AGP) on the negative sense genome RNA. The P gene encodes for two additional non-structural proteins, namely C and V. The V protein is produced due to co-transcriptional P mRNA editing by insertion of non-template G residues at an editing site. The C protein is produced from an alternative reading frame downstream of the P initiation codon. Expression of C occurs following leaky scanning by the polymerase that reads through the first ATG and initiates at the second ATG.

Fig. 4

A schematic replication of life cycle of a morbillivirus (adapted from Moss and Griffin, 2006). The first step in virus infection is the attachment of a virion to a host cell surface receptor which leads to the fusion of viral and cellular membrane. The negative sense RNA genome is released into the cell cytoplasm and transcription initiates to produce viral gene transcripts (mRNAs), which are translated using the host cell transcriptional machinery. Later, following the production of the necessary viral proteins, a switch to a replicative mode occurs that results in the production of a positive sense (+) viral complementary RNA (vcRNA +ve), a replicative intermediate which acts as a template for the generation of progeny negative sense genome RNA. The encapsidated genomes interact with the M protein and the viral glycoproteins, leading to budding of new virions at the host cell plasma membrane. ER: endoplasmic reticulum.

Fig. 5

Global spread of Peste des petits ruminants virus from its first detection in 1942–2014, including lineage distribution (a: adopted from Food and Agriculture Organisation (FAO, 2009), b: recent circulations of Peste des petits ruminants virus in Africa, drawn by using smart draw software).

Fig. 6

Time-scaled Bayesian MCC phylogeny tree based on Peste des petits ruminants virus complete genome sequences; the tree was constructed using the UCED model and exponential tree prior (branch tips correspond to the date of collection, branch lengths reflect elapsed time—tree nodes are annotated with posterior probability values, estimated median dates of TMRCA and the corresponding 95% HPD interval values of TMRCA indicated as grey bars; the horizontal axis indicates time in years).

Fig. 7

Immunohistochemical staining of Peste des petits ruminants virus antigen in experimentally infected goats. (a) Predominately peripheral paracortical immunolabelling of syncytia within the LPSLN (7 days post-infection); dendritic-type cells present and positive for virus antigen (arrow) with an infected lymphocyte also present (open arrow). (b) Advanced epithelial infection of the pharyngeal tonsil (7 days post-infection) with syncytia formation. (c) Conjunctival mucosal epithelium (9 days post-infection); evidence of advanced epithelial and proprial infection involving a mixed population of inflammatory and epithelial cells around an exocrine gland (arrows); immunolabelling within the proprial lymphoid follicle circumscribed by this gland (open arrow). (d) Labial mucosal epithelium (9 days post-infection) with a large epithelial syncytium (arrow) seen in the lower stratum spinosum layer. (e) Severe abomasal infection (9 days post-infection) of crypt epithelial cells (arrows). (f) Marked viral infection of both glandular epithelial cells and the immune/inflammatory cells present within the caecum (7 days post-infection). Scale bars represent 100 μm. Adapted from Pope et al. (2013).

Fig. 8

Expression of Peste des petits ruminants virus (PPRV) N and H proteins and/or GFP with C77 mAb binding activity in the virus recombinants (positive and negative marker vaccine strains) and parental virus infected cells; VDS cells were infected with viruses at an MOI of 0.01 and fixed 24 h post-infection using 4% paraformaldehyde; cells were stained separately with primary antibodies of mouse anti PPRV H (C77) and mouse anti PPRV N (C11) followed by secondary antibody Alexa Fluor 488 goat anti-mouse (red); cell nuclei were stained with DAPI (blue) and GFP autoflorescence (green); expression pattern of the virus N and H proteins were comparable between the recombinant and parental virus. The anti-PPRV H-mAb could not detect mutated H-protein in rPPRV-C77 infected cells. Autoflorescence of GFP was observed in the rescued rPPRV + GFP (an image with the autoflorescence to show GFP was not taken alongside N antibody staining). Adapted from Muniraju et al. (2014b). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.).