5 Peste des Petits Ruminants Virus Muhammad Munir The Pirbright Institute, Compton Laboratory, Compton, UK 5.1 Introduction 5.2 PPRV Identification and Historical Perspective Peste des petits ruminants (PPR) is a highly contagious, fatal and economically impor- Officially, PPR was first described in the tant disease of both domestic and wild Republic of Côte d’Ivoire in West Africa in small ruminants, and camels. Owing to high 1942 (Gargadennec and Lalanne, 1942), morbidity (100%) and mortality (90%), PPR however, there are indications that the dis- was included in the OIE (Office International ease existed much earlier. Since PPR and RP des Epizooties) list of notifiable terrestrial are clinically related diseases and the animal diseases. The disease is currently viruses are antigenically similar, it is spreading rapidly in most countries of the believed that PPR remained undiagnosed sub-Saharan and North Africa, the Middle due to the high prevalence of RP and the East and Indian sub-continent and as far as inability of the available diagnostic tests to into Tibet, China. differentiate PPR from RP (Baron et al., During the rinderpest virus (RPV) 2011). Furthermore, it is likely that, owing eradication campaign, there have been to cross-neutralization between PPRV and significant improvements in understand- RPV, small ruminants infected with RPV ing the biology of viruses; however, the would have developed protective antibod- primary focus has remained developing ies suppressing the clinical outcome of and improving efficient vaccines. The pre- PPRV infection (Taylor, 1979). Nevertheless, sent chapter aims to provide an overview of the disease gained attention when a severe all known features of the PPRV genome, rinderpest-like disease was observed in structure and biology. The structural and sheep and goats, which was unable to trans- non-structural proteins are described mit to the cattle reared in the same herd or comprehensively. Additionally, available in the close vicinity. Initially, different diagnostic tests and potent PPRV vaccines names such as ‘kata’, ‘pseudo rinderpest’, are discussed and finally current chal- ‘syndrome of stomatitis-pneumoenteritis’ lenges and future possibilities for disease and ‘ovine rinderpest’ were used to describe eradication are highlighted. the disease. Later, a French name, ‘peste des © CAB International 2013. Mononegaviruses of Veterinary Importance Vol. I: Pathobiology and Molecular Diagnosis (ed. M. Munir) 65 66 M. Munir petits ruminants’, was suggested because of in West Africa, where PPRV once originated. its clinical, pathological and immunologi- Lineage III is restricted to the Middle East cal similarities with RPV. At the time of first and East Africa. Though lineage IV was PPRV recognition, it was considered a vari- strictly considered an Asian lineage, it is ant of RPV. However, Gibbs et al. (1979) now overwhelming the other lineages in revealed that PPRV is biologically and phys- African countries, while still being predomi- ico-chemically distinct and is therefore a nant in Asia (Kwiatek et al., 2011; Munir new member in the genus Morbillivirus, et al., 2013) (Fig. 5.1). Most recent reports of along with RPV, canine and phocine distem- PPRV in previously PPRV-free countries per viruses (CDV and PDV), measles virus belong to lineage IV, which suggests that lin- (MV) and morbilliviruses of porpoises, dol- eage IV is a novel group of PPRV and may phins and cetaceans (PMV, DMV and CMV). replace the other lineages in the near future. It is also likely that only lineage IV is cur- rently causing outbreaks. Moreover, it is cru- cial to note that countries once exclusively 5.3 Geographical Distribution carrying a single lineage are now simultane- ously reporting the presence of several line- After first identification, PPRV spread to sub- ages, i.e. Sudan and Uganda (Kwiatek et al., Saharan Africa, the Middle East, Turkey and 2011; Luka et al., 2012). In the majority of the Indian subcontinent. During the last dec- cases, the newly introduced lineage is line- ade, the disease has been reported for the first age IV (Kwiatek et al., 2011; Luka et al., time in China, Kenya, Uganda, Tanzania, 2012; Cosseddu et al., 2013). Morocco and Tunisia (Banyard et al., 2010; Munir et al., 2013). This demonstrates that the virus is highly infectious, and is of emerg- 5.4 Economic Impact of PPR Disease ing transboundary nature. Initially, PPRV was characterized and phylogenetically analysed PPR is generally considered a major con- based on the fusion gene (F), which classified straint for small ruminant production; how- all the strains of PPRV into four distinct line- ever, the economic impact of the disease has ages (Shaila et al., 1996; Dhar et al., 2002). not been fully evaluated (Ezeokoli et al., Later, it appeared that phylogenetic analysis 1986; Rossiter and Taylor, 1994; Nanda et al., based on the nucleoprotein gene (N) pre- 1996). The economic importance of PPR is sented a better molecular epidemiological pat- primarily due to its highly contagious nature, tern (Kwiatek et al., 2007) and is currently with a case fatality rate as high as 100%. This preferred over F gene-based phylogenetic is of particular concern for the economics of analysis. However, all the PPRV strains small rural farms, where sheep and goats are remained in the same group regardless of reared as the sole source of income. Moreover, what gene was used as basis for classification, PPR is most prevalent in countries that rely except that the F gene-based lineage I (i.e. heavily on subsistence farming of small Nig/75) became lineage II on the N gene-based ruminants for trade and food supply. tree. Recently, Balamurugan et al. (2010) sug- The disease consequences can be pre- gested that the use of the haemagglutinin- vented by the use of highly efficacious vaccine. neuraminidase (HN) gene, in addition to the F It has been calculated that an investment of and N genes, could give better resolution and US$2 million can bring a return of US$24 permit tracing of virus transmission within million. This estimation has been made on outbreaks. Nevertheless, it is still unclear 1 million animals (Stem, 1993). These facts whether differences between lineages merely lead to the perception that PPR is one of the reflect geographical speciation or if they are top ten diseases in sheep and goats that are also correlated with variability in pathogen- having a high impact on the poor rural small icity between isolates (Banyard et al., 2010). ruminant farmers (Perry et al., 2002). PPRV belonging to lineages I and II have Collectively, it was estimated that PPR exclusively been isolated from the countries causes a loss of US$1.5 million annually in Peste des Petits Ruminants Virus 67 99 Nigeria/76/1(DQ840164) Ghana/Accra/78(DQ840167) 82 Ghana/Ghana/78(DQ840166) Lineage II 98 African lineage II Nigeria/75/2(DQ840161) Mali/99/366(DQ840193) 99 Pakistan/Multan/2010(JN009674) 76 Pakistan/Faisalabad/2010(JN009673) Tajikistan/04(DQ840198) China/Tibet/07(EU360596) Iran/98/3(DQ840186) Lineage IV Israel/Arbella/93(DQ840173) 91 98 Saudi Arabia/99/7(DQ840195) Iran/98/4(DQ840187) Israel/98/2(DQ840188) India/94(DQ840176) 94 India/Tamilnadu/95/2(DQ840182) India/Pradesh/95 1(DQ840178) Asian lineage IV Israel/95/3(DQ840181) Turkey/96(DQ840184) India/Sassayan/94/2(DQ840179) 87 Saudi Arabia/99/8(DQ840197) Lineage I Senegal/68(DQ840165) Guinea//88(DQ840170) 99 Cote dIvoire/ICV/89(EU267273) 98 Burkina Faso/88(DQ840172) Senegal/94(DQ840174) 92 89 Guinea-Bissau/Bissau/89(DQ840171) Lineage III Ethiopia/94(DQ840175) Ethiopia/96(DQ840183) 100 100 Oman/Ibri/83(DQ840168) African lineage I UAE/Dorcas/86(DQ840169) Sudan/Sinar/72(DQ840158) 78 Sudan/Mielik/72(DQ840159) 0.02 African lineage III Fig. 5.1. Phylogenetic analysis of PPR isolates based on the N gene. The distribution of different lineages is detailed by shading the maps for each lineage. Nigeria (Hamdy et al., 1976), US$39 million 5.5 Virion Morphology, Structural in India (Bandyopadhyay, 2002) and at least US$1.5 million in Iran (Bazarghani et al., and Accessory Proteins 2006) and US$15 million in Kenya (Thombare and Sinha, 2009). Besides these 5.5.1 PPR virions figures, the worldwide economic impact of PPR largely remains elusive, and a well- Like other paramyxoviruses, PPR virions are planned cost-benefit analysis of PPR versus enveloped, pleomorphic particles (Fig. 5.2A) policy responses that includes both the and are comprised of single-stranded RNA direct and indirect impacts associated with genome with negative polarity. The length PPR is required. of the entire genome of PPRV is 15,948 68 M. Munir nucleotides, which is the second longest endonuclease digestion. The RNP strands among all morbilliviruses after a recently appear as a herring bone with a thickness of characterized feline morbillivirus (Bailey ~14–23 nm (Fig. 5.2B) (Durojaiye et al., 1985). et al., 2005; Woo et al., 2012). The diameter Each molecule of N protein is associated with of PPR virions ranges from 400 to 500 nm. the six nucleotides of the genome, which The phosphoprotein (P) acts as a co-factor explains the requirement of ‘the rule of six’ of large protein (L), which is the viral RNA for paramyxoviruses including PPRV (Lamb dependent RNA polymerase (RdRp). There and Kolakofsky, 2001). Contrary to this are three proteins associated with the host strongly accepted belief, it was revealed that cell membrane-derived viral envelope. The PPRV obey the rule of six but carry a degree matrix (M) protein acts as a link, which of flexibility. By a still unknown mechanism, associates with the nucleocapsid and the transcription and replication in PPRV mini- two external viral proteins, the fusion (F) genome can accommodate some deviation in protein and the HN protein.