Investigation of Peste des petits ruminants virus circulation in Uttarakhand, India: a step towards global eradication of PPR by 2030.

This study was conducted to estimate the seroprevalence of Peste des petits ruminants virus (PPRV) and to determine the virus distribution in unvaccinated goats in the Pantnagar region of Uttarakhand state, India. A total of 212 serum samples from goats were collected randomly from various villages in three districts (Udhamsingh Nagar, Nainital, and Almora) of Uttarakhand. Serum samples were tested for anti-PPRV antibodies by a commercially available kit. RNA was extracted from the clinical samples and it was subjected to one-step RT-PCR, followed by virus isolation from positive samples. A total of 41 animals from various villages were found to be seropositive with a prevalence rate of 19.33%. PPR outbreaks were also reported from the Tarai region of Uttarakhand, and detection by PCR confirmed PPRV in 8 goats. Two representative swab samples were subjected to virus isolation in Vero cells and both samples showed typical cytopathic effects. The present study shows that PPRV is circulating in the Tarai region of Uttarakhand and mass vaccination for PPR must be followed in this region to increase herd immunity to a protective level. To the best of our knowledge, this is the first investigation of PPRV seroprevalence in unvaccinated goats of Uttarakhand, India.

Vimentin inhibits peste des petits ruminants virus replication by interaction with nucleocapsid protein.

The Peste des petits ruminant virus (PPRV) is a member of the Paramyxoviridae family and is classified into the genus Measles virus. PPRV predominantly infects small ruminants, leading to mortality rates of nearly 100%, which have caused significant economic losses in developing countries. Host proteins are important in virus replication, but the PPRV nucleocapsid (N) protein-host interacting partners for regulating PPRV replication remain unclear. The present study confirmed the interaction between PPRV-N and the host protein vimentin by co-immunoprecipitation and co-localization experiments. Overexpression of vimentin suppressed PPRV replication, whereas vimentin knockdown had the opposite effect. Mechanistically, N was subjected to degradation via the ubiquitin/proteasome pathway, where vimentin recruits the E3 ubiquitin ligase NEDD4L to fulfill N-ubiquitination, resulting in the degradation of the N protein. These findings suggest that the host protein vimentin and E3 ubiquitin ligase NEDD4L have an anti-PPRV effect.

Plasminogen activator urokinase interacts with the fusion protein and antagonizes the growth of Peste des petits ruminants virus.

Peste des petits ruminants is an acute and highly contagious disease caused by the Peste des petits ruminants virus (PPRV). Host proteins play a crucial role in viral replication. However, the effect of fusion (F) protein-interacting partners on PPRV infection is poorly understood. In this study, we found that the expression of goat plasminogen activator urokinase (PLAU) gradually decreased in a time- and dose-dependent manner in PPRV-infected goat alveolar macrophages (GAMs). Goat PLAU was subsequently identified using co-immunoprecipitation and confocal microscopy as an F protein binding partner. The overexpression of goat PLAU inhibited PPRV growth and replication, whereas silencing goat PLAU promoted viral growth and replication. Additionally, we confirmed that goat PLAU interacted with a virus-induced signaling adapter (VISA) to antagonize F-mediated VISA degradation, increasing the production of type I interferon. We also found that goat PLAU reduced the inhibition of PPRV replication in VISA-knockdown GAMs. Our results show that the host protein PLAU inhibits the growth and replication of PPRV by VISA-triggering RIG-I-like receptors and provides insight into the host protein that antagonizes PPRV immunosuppression.IMPORTANCEThe role of host proteins that interact with Peste des petits ruminants virus (PPRV) fusion (F) protein in PPRV replication is poorly understood. This study confirmed that goat plasminogen activator urokinase (PLAU) interacts with the PPRV F protein. We further discovered that goat PLAU inhibited PPRV replication by enhancing virus-induced signaling adapter (VISA) expression and reducing the ability of the F protein to degrade VISA. These findings offer insights into host resistance to viral invasion and suggest new strategies and directions for developing PPR vaccines.

A Morbillivirus Infection Shifts DC Maturation Toward a Tolerogenic Phenotype to Suppress T Cell Activation.

Viruses have evolved numerous strategies to impair immunity so that they can replicate more efficiently. Among those, the immunosuppressive effects of morbillivirus infection can be particularly problematic, as they allow secondary infections to take hold in the host, worsening disease prognosis. In the present work, we hypothesized that the highly contagious morbillivirus peste des petits ruminants virus (PPRV) could target monocytes and dendritic cells (DC) to contribute to the immunosuppressive effects produced by the infection. Monocytes isolated from healthy sheep, a natural host of the disease, were able be infected by PPRV and this impaired the differentiation and phagocytic ability of immature monocyte-derived DC (MoDC). We also assessed PPRV capacity to infect differentiated MoDC. Ovine MoDC could be productively infected by PPRV, and this drastically reduced MoDC capacity to activate allogeneic T cell responses. Transcriptomic analysis of infected MoDC indicated that several tolerogenic DC signature genes were upregulated upon PPRV infection. Furthermore, PPRV-infected MoDC could impair the proliferative response of autologous CD4+ and CD8+ T cell to the mitogen concanavalin A (ConA), which indicated that DC targeting by the virus could promote immunosuppression. These results shed new light on the mechanisms employed by morbillivirus to suppress the host immune responses. IMPORTANCE Morbilliviruses pose a threat to global health given their high infectivity. The morbillivirus peste des petits ruminants virus (PPRV) severely affects small-ruminant-productivity and leads to important economic losses in communities that rely on these animals for subsistence. PPRV produces in the infected host a period of severe immunosuppression that opportunistic pathogens exploit, which worsens the course of the infection. The mechanisms of PPRV immunosuppression are not fully understood. In the present work, we demonstrate that PPRV can infect professional antigen-presenting cells called dendritic cells (DC) and disrupt their capacity to elicit an immune response. PPRV infection promoted a DC activation profile that favored the induction of tolerance instead of the activation of an antiviral immune response. These results shed new light on the mechanisms employed by morbilliviruses to suppress the immune responses.

Comparative pathogenesis of peste des petits ruminants virus strains of difference virulence.

Peste des petits ruminants (PPR) is an acute disease of small ruminants caused by a morbillivirus. Clinical observation of the disease in the field revealed that several species of small ruminants are affected to varying degrees. This difference in disease-related effects could depend either on the host or on the virulence of the virus strain. A previous study highlighted the difference in virulence between two strains of PPRV used to infect Saanen goats. For this breed, PPRV Morocco 2008 strain (MA08) was highly virulent while PPRV Côte d'Ivoire 1989 (IC89) strain induced mild disease. Experimental studies generally based on healthy and young animals do not permit exploration of the natural variability of the host susceptibility to PPRV. Therefore, building on the previous study on Saanen goats, the current study focussed on this breed of goat and used commercially available animals with an unknown history of infection with other pathogens. Results confirmed the previous disease pattern for PPRV IC89 and MA08 strains. Viral RNA detection, macroscopic and histological lesions were stronger for the highly virulent MA08 strain. We show here for the first time that viral RNA can be detected in the tissues of vaccinated animals. Viral RNA was also detected for the first time in serum samples, which is in agreement with the role of circulating immune cells in transporting the virus into host target organs. Thus, this study provides insight into the pathogenesis of strains of different virulence of PPRV and will help to better understand the onset of the disease.

PPRV-Induced Autophagy Facilitates Infectious Virus Transmission by the Exosomal Pathway.

Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. We showed previously that PPRV induced sustained autophagy for their replication in host cells. Many studies have shown that exosomes released from virus-infected cells contain a variety of viral and host cellular factors that are able to modulate the recipient's cellular response and result in productive infection of the recipient host. Here, we show that PPRV infection results in packaging of the viral genomic RNA and partial viral proteins into exosomes of Vero cells and upregulates exosome secretion. We provide evidence showing that the exosomal viral cargo can be transferred to and establish productive infection in a new target cell. Importantly, our study reveals that PPRV-induced autophagy enhances exosome secretion and exosome-mediated virus transmission. Additionally, our data show that TSG101 may be involved in the sorting of the infectious PPRV RNA into exosomes to facilitate the release of PPRV through the exosomal pathway. Taken together, our results suggest a novel mechanism involving autophagy and exosome-mediated PPRV intercellular transmission. IMPORTANCE Autophagy plays an important role in PPRV pathogenesis. The role of exosomes in viral infections is beginning to be appreciated. The present study examined the role of autophagy in secretion of infectious PPRV from Vero cells. Our data provided the first direct evidence that ATG7-mediated autophagy enhances exosome secretion and exosome-mediated PPRV transmission. TSG101 may be involved in the sorting of the infectious PPRV RNA genomes into exosomes to facilitate the release of PPRV through the exosomal pathway. Inhibition of PPRV-induced autophagy or TSG101 expression could be used as a strategy to block exosome-mediated virus transmission.

Retrospective Characterization of Initial Peste des petits ruminants Outbreaks (2008-2012) in the Democratic Republic of the Congo.

Peste des petits ruminants (PPR) is an acute, contagious viral disease of small ruminants, goats and sheep. The Democratic Republic of the Congo (DRC) was a PPR-free country until 2007, although in 2006, scare alerts were received from the east and the southwest of the country, reporting repeated mortalities, specifically in goats. In 2008, PPR outbreaks were seen in several villages in the west, leading to structured veterinary field operations. Blood, swabs and pathological specimens consisting of tissues from lungs, spleens, lymph nodes, kidneys, livers and hearts were ethically collected from clinically infected and/or dead animals, as appropriate, in 35 districts. Epidemiological information relating to major risk factors and socio-economic impact was progressively collected, revealing the deaths of 744,527 goats, which converted to a trade value of USD 35,674,600. Samples from infected and dead animals were routinely analyzed by the Central Veterinary Laboratory at Kinshasa for diagnosis, and after official declaration of PPR outbreaks by the FAO in July 2012, selected tissue samples were sent to The Pirbright Institute, United Kingdom, for genotyping. As a result of surveys undertaken between 2008 and 2012, PPR virus (PPRV)-specific antibodies were detected in 25 locations out of 33 tested (75.7%); PPRV nucleic acid was detected in 25 locations out of 35 (71.4%); and a typical clinical picture of PPR was observed in 23 locations out of 35 (65.7%). Analysis of the partial and full genome sequences of PPR viruses (PPRVs) obtained from lymphoid tissues of dead goats collected in Tshela in the DRC in 2012 confirmed the circulation of lineage IV PPRV, showing the highest homology (99.6-100%) with the viruses circulating in the neighboring countries of Gabon, in the Aboumi outbreak in 2011, and Nigeria (99.3% homology) in 2013, although recent outbreaks in 2016 and 2018 in the western part of the DRC that borders with East Africa demonstrated circulation of lineage II and lineage III PPRV.

Pheno- and genotypic characterization and identification of novel subtypes of Peste des Petits Ruminants virus in domestic and captive wild goats in Northern Iraq.

BACKGROUND: Peste des Petits Ruminants (PPR) is an acute or peracute contagious transboundary viral disease that mainly affects caprine and ovine and causes significant economic impact in developing countries. After two PPR virus outbreaks in 2011 and 2014, an investigation, from August 2015 to September 2016, was carried out in Northern Iraq when an increased morbidity and mortality rates were reported in the domestic and captive wild goats. In the present study, ten domestic goat farms and seven captive wild goat herds located in seven geographical areas of Northern Iraq were clinically, pathologically, serologically and genotypically characterized to determine the prevalence and potential cause of PPR virus outbreak. RESULTS: The outbreak occurred with rate of morbidity (26.1%) and mortality (11.1%) in domestic goat farms as compared to captive wild goat herds where relatively high mortality (42.9%) and low morbidity (10.9%) rates were recorded. Based on the clinical symptoms (mucopurulent nasal discharges, ulceration and erosion of oral mucosa, profuse watery diarrhea) and necropsy (hemorrhage and congestion on mucous membranes of the colon and rectum with zebra stripes lesions) results, overall, the serological test findings revealed a high frequency (47.9%) of positive samples for anti-PPRV nucleoprotein antibodies. Furthermore, the nucleoprotein (N) gene was detected in 63.2 and 89.1% of samples using conventional and reverse transcription real-time quantitative PCR assays. A phylogenetic analysis of N gene amino acid sequences clustered with the reference strain revealed lineage IV similar to the strains isolated in 2011 and 2014, respectively. However, two sub-types of lineage IV (I and II), significantly distinct from the previous strains, were also observed. CONCLUSION: The phylogenetic analysis suggests that movements of goats are possible cause and one of the important factors responsible for the spread of virus across the region. The study results would help in improving farm management practices by establishing a PPR virus eradication program using regular monitoring and vaccination program to control and mitigate the risk of re-emergence of PPR virus infection in domestic and captive wild goats in Iraq.

Molecular insights into peste des petits ruminants virus identified in Bangladesh between 2008 and 2020.

An in-depth knowledge of the molecular evolution of the peste des petits ruminants virus (PPRV) is critical for the success of the current global eradication program. For this reason, a molecular evolutionary analysis of PPRVs circulating in Bangladesh over a decade (2008-2020) was performed. The complete genome sequencing of three PPRV isolates from 2008 (BD2), 2015 (BD12) and 2017 (BD17) as well as full length nucleocapsid (N), matrix (M) and fusion (F) gene sequencing of seven more samples from 2015 to 2020 was performed. Phylogenetic analysis classified all ten PPRVs from Bangladesh as members of lineage IV and showed that they were closely related to PPRV strains detected in China and Tibet during 2007-2008, and India during 2014-2018. Time scale Bayesian Maximum Clade Credibility (MCC) phylogenetic analysis of the three complete genomes revealed a mean Time to Most Recent Common Ancestor (TMRCA) of 2000. Comparative deduced amino acid residue analysis at various functional motifs of PPRVs related to virus structure and function, virulence and host adaptation, receptor binding sites and polymerase activity revealed conserved residues among the PPRVs from Bangladesh. In total sixteen epitopes were predicted from four immunogenic proteins i.e. N, M, F and haemagglutinin (H). Interestingly, the predicted epitopes from the N and M proteins shared conserved epitopes with two vaccine strains currently being used, indicating that the strains from Bangladesh could be potentially used as alternative local vaccines.

Ongoing Assessment of the Molecular Evolution of Peste Des Petits Ruminants Virus Continues to Question Viral Origins.

Understanding the evolution of viral pathogens is critical to being able to define how viruses emerge within different landscapes. Host susceptibility, which is spread between different species and is a contributing factor to the subsequent epidemiology of a disease, is defined by virus detection and subsequent characterization. Peste des petits ruminants virus is a plague of small ruminant species that is a considerable burden to the development of sustainable agriculture across Africa and much of Asia. The virus has also had a significant impact on populations of endangered species in recent years, highlighting its significance as a pathogen of high concern across different regions of the globe. Here, we have re-evaluated the molecular evolution of this virus using novel genetic data to try and further resolve the molecular epidemiology of this disease. Viral isolates are genetically characterized into four lineages (I-IV), and the historic origin of these lineages is of considerable interest to the molecular evolution of the virus. Our re-evaluation of viral emergence using novel genome sequences has demonstrated that lineages I, II and IV likely originated in West Africa, in Senegal (I) and Nigeria (II and IV). Lineage III sequences predicted emergence in either East Africa (Ethiopia) or in the Arabian Peninsula (Oman and/or the United Arab Emirates), with a paucity of data precluding a more refined interpretation. Continual refinements of evolutionary emergence, following the generation of new data, is key to both understanding viral evolution from a historic perspective and informing on the ongoing genetic emergence of this virus.

Exchange of C-Terminal Variable Sequences within Morbillivirus Nucleocapsid Protein Are Tolerated: Development and Evaluation of Two Marker (DIVA) Vaccines (Sungri/96 DIVA, Nigeria/75/1 DIVA) against PPR.

Across Africa, the Middle East, and Asia, peste des petits ruminants virus (PPRV) places a huge disease burden on agriculture, affecting, in particular, small ruminant production. The recent PPR outbreaks in Northern Africa, the European part of Turkey, and Bulgaria represent a significant threat to mainland Europe, as a source of disease. Although two safe and efficacious live attenuated vaccines (Sungri/96 and Nigeria/75/1) are available for the control of PPR, current serological tests do not enable the differentiation between naturally infected and vaccinated animals (DIVA). The vaccinated animals develop a full range of immune responses to viral proteins and, therefore, cannot be distinguished serologically from those that have recovered from a natural infection. This poses a serious problem for the post-vaccinal sero-surveillance during the ongoing PPR eradication program. Furthermore, during the latter stages of any eradication program, vaccination is only possible if the vaccine used is fully DIVA compliant. Using reverse genetics, we have developed two live attenuated PPR DIVA vaccines (Sungri/96 DIVA and Nigeria/75/1 DIVA), in which the C-terminal variable region of the PPRV N-protein has been replaced with dolphin morbillivirus (DMV). As a proof of principle, both the DIVA vaccines were evaluated in goats in pilot studies for safety and efficacy, and all the animals were clinically protected against the intranasal virulent virus challenge, similar to the parent vaccines. Furthermore, it is possible to differentiate between infected animals and vaccinated animals using two newly developed ELISAs. Therefore, these DIVA vaccines and associated tests can facilitate the sero-monitoring process and speed up the implementation of global PPR eradication through vaccination.

Identification of Differential Responses of Goat PBMCs to PPRV Virulence Using a Multi-Omics Approach.

Peste des petits ruminants (PPR) is an acute transboundary infectious viral disease of small ruminants, mainly sheep and goats. Host susceptibility varies considerably depending on the PPR virus (PPRV) strain, the host species and breed. The effect of strains with different levels of virulence on the modulation of the immune system has not been thoroughly compared in an experimental setting so far. In this study, we used a multi-omics approach to investigate the host cellular factors involved in different infection phenotypes. Peripheral blood mononuclear cells (PBMCs) from Saanen goats were activated with a T-cell mitogen and infected with PPRV strains of different virulence: Morocco 2008 (high virulence), Ivory Coast 1989 (low virulence) and Nigeria 75/1 (live attenuated vaccine strain). Our results showed that the highly virulent strain replicated better than the other two in PBMCs and rapidly induced cell death and a stronger inhibition of lymphocyte proliferation. However, all the strains affected lymphocyte proliferation and induced upregulation of key antiviral genes and proteins, meaning a classical antiviral response is orchestrated regardless of the virulence of the PPRV strain. On the other hand, the highly virulent strain induced stronger inflammatory responses and activated more genes related to lymphocyte migration and recruitment, and inflammatory processes. Both transcriptomic and proteomic approaches were successful in detecting viral and antiviral effectors under all conditions. The present work identified key immunological factors related to PPRV virulence in vitro.

Inhibiting pyrimidine biosynthesis impairs Peste des Petits Ruminants Virus replication through depletion of nucleoside pools and activation of cellular immunity.

Replication of peste des petits ruminants virus (PPRV) strongly depends on the cellular environment and resources of host cells including nucleoside pool. Thus, enzymes involved in nucleoside biosynthesis (such as pyrimidine biosynthesis pathway) are regarded as attractive targets for antiviral drug development. Here, we demonstrate that brequinar (BQR) and leflunomide (LFM) which are two specific inhibitors of DHODH enzyme and 6-azauracil (6-AU) which is an ODase enzyme inhibitor robustly inhibit PPRV replication in HEK293T cell line as well as in peripheral blood mononuclear cells isolated from goat. We further demonstrate that these agents exert anti-PPRV activity via the depletion of purimidine nucleotide. Interestingly, these inhibitors can trigger the transcription of antiviral interferon-stimulated genes (ISGs). However, the induction of ISGs is largely independent of the classical JAK-STAT pathway. Combination of BQR with interferons (IFNs) exerts enhanced ISG induction and anti-PPRV activity. Taken together, this study reveals an unconventional novel mechanism of crosstalk between nucleotide biosynthesis pathways and cellular antiviral immunity in inhibiting PPRV replication. In conclusion, targeting pyrimidine biosynthesis represents a potential strategy for developing antiviral strategies against PPRV.

Gender and intersectional analysis of livestock vaccine value chains in Kaffrine, Senegal.

Among livestock species, poultry and small ruminants are of particular importance to rural women in low- and middle-income countries, as means to generate income, provide nutritious food for the family, accumulate wealth, and confer social status. Newcastle disease (ND) and Peste des Petits Ruminants (PPR) are widespread livestock diseases of poultry and small ruminants, respectively. While both diseases are vaccine preventable, numerous constraints limit the availability of and access to livestock vaccines, especially among the most vulnerable populations in developing countries. The literature on equity and effectiveness of livestock vaccine distribution systems has emphasized many of these constraints, however a gendered analysis and deeper understanding of the vaccine system remain insufficient. This paper applies a gendered and intersectional transformational approach, or GITA, to highlight how gender and other social factors affect the provision and utilization of vaccines for ND and PPR diseases in the region of Kaffrine, Senegal. We first articulate and describe the vaccine value chains (VVCs) for these diseases in Kaffrine, and then analyze the gendered and intersectional dynamics at different nodes of the VVCs, including actors at the national level, through the regional and district levels, down to providers of animal health at community level and the livestock keepers themselves. Our findings indicate that actors' various experiences are shaped and defined mainly by rigid gender norms, location and remoteness, and to a lesser degree by other social stratifications of age, ethnicity, and livelihood. Given the significant role that gender norms play in the livestock vaccine value chains, differences according to the livestock species, regulation of vaccine administration, and vaccine distribution systems emerge as highly relevant for understanding barriers that women specifically face within the livestock vaccination system.

Peste des Petits Ruminants Virus Infection at the Wildlife-Livestock Interface in the Greater Serengeti Ecosystem, 2015-2019.

Peste des petits ruminants (PPR) is a viral disease of goats and sheep that occurs in Africa, the Middle East and Asia with a severe impact on livelihoods and livestock trade. Many wild artiodactyls are susceptible to PPR virus (PPRV) infection, and some outbreaks have threatened endangered wild populations. The role of wild species in PPRV epidemiology is unclear, which is a knowledge gap for the Global Strategy for the Control and Eradication of PPR. These studies aimed to investigate PPRV infection in wild artiodactyls in the Greater Serengeti and Amboseli ecosystems of Kenya and Tanzania. Out of 132 animals purposively sampled in 2015-2016, 19.7% were PPRV seropositive by ID Screen PPR competition enzyme-linked immunosorbent assay (cELISA; IDvet, France) from the following species: African buffalo, wildebeest, topi, kongoni, Grant's gazelle, impala, Thomson's gazelle, warthog and gerenuk, while waterbuck and lesser kudu were seronegative. In 2018-2019, a cross-sectional survey of randomly selected African buffalo and Grant's gazelle herds was conducted. The weighted estimate of PPRV seroprevalence was 12.0% out of 191 African buffalo and 1.1% out of 139 Grant's gazelles. All ocular and nasal swabs and faeces were negative by PPRV real-time reverse transcription-polymerase chain reaction (RT-qPCR). Investigations of a PPR-like disease in sheep and goats confirmed PPRV circulation in the area by rapid detection test and/or RT-qPCR. These results demonstrated serological evidence of PPRV infection in wild artiodactyl species at the wildlife-livestock interface in this ecosystem where PPRV is endemic in domestic small ruminants. Exposure to PPRV could be via spillover from infected small ruminants or from transmission between wild animals, while the relatively low seroprevalence suggests that sustained transmission is unlikely. Further studies of other major wild artiodactyls in this ecosystem are required, such as impala, Thomson's gazelle and wildebeest.

Detection of peste des petits ruminants virus in pneumonic lungs from clinically apparently healthy camels slaughtered at Tambul slaughterhouse, Central Sudan.

The study investigated the presence and prevalence of peste des petits ruminants (PPR) viral antigens among camels in Tambul area, Gezira State, Central Sudan, regardless of its sex, age and breed, and their possible contribution in the epidemiology of the disease in the Sudan. Hundred pneumonic lung tissues were aseptically collected from clinically apparently healthy camels showed no signs of illness at ante-mortem examination, from Tambul slaughterhouse, Tambul area, Gezira State, Central Sudan, between November and December 2018. Samples were collected based on presence of the pneumonic signs, at the tissue level, including congestion of the lungs, presence of abscesses, fragility, changes in colour and thickness of the tissue. In order to detect PPR viral antigen, haemagglutination (HA) test was employed on lung tissue homogenate, using chicken RBCs suspension, which gave a positive reaction in 17-19 min. PPRV antigen was detected in 98 of camel samples with an overall antigenic prevalence of 98%. Of note, the HA titres achievable ranged from 4 to 256 HA units (HAU) with mean titre of 14.4 HAU, whereas apparently most of the samples achieved HA titres of 8 HAU. The results demonstrated presence of PPR viral antigens associated with pneumonia in camels indicating exposure of these camels to PPRV and probably presence of subclinical infection. Infection of species other than small ruminants suggests the fact that camels are potential hosts for PPRV and might play a role (or not) in the epidemiology of the disease. Further studies are needed to demonstrate if camels are able to transmit PPRV for in-contact small ruminants or other animal species.

Peste des petits ruminants virus non-structural C protein inhibits the induction of interferon-ß by potentially interacting with MAVS and RIG-I.

Peste des petits ruminants virus (PPRV) causes an acute and highly contagious disease in domestic and wild small ruminants throughout the world, mainly by invoking immunosuppression in its natural hosts. It has been suggested that the non-structural C protein of PPRV helps in evading host responses but the molecular mechanisms by which it antagonizes the host responses have not been fully characterized. Here, we report the antagonistic effect of PPRV C protein on the expression of interferon-ß (IFN-ß) through both MAVS and RIG-I mediated pathways in vitro. Dual luciferase reporter assay and direct expression of IFN-ß mRNA analysis indicated that PPRV C significantly down regulates IFN-ß via its potential interaction with MAVS and RIG-I signaling molecules. Results further indicated that PPRV C protein significantly suppresses endogenous and exogenous IFN-ß-induced anti-viral effects in PPRV, EMCV and SVS infections in vitro. Moreover, PPRV C protein not only down regulates IFN-ß but also the downstream cytokines of interferon stimulated genes 56 (ISG56), ISG15, C-X-C motif chemokine (CXCL10) and RIG-I mediated activation of IFN promoter elements of ISRE and NF-κB. Further, this study deciphers that PPRV C protein could significantly inhibit the phosphorylation of STAT1 and interferes with the signal transmission in JAK-STAT signaling pathway. Collectively, this study indicates that PPRV C protein is important for innate immune evasion and disease progression.

Growth kinetics of a Vero cells adapted Bangladeshi strain of peste des petits ruminants (PPR) virus in cell culture.

Growth kinetics of a Vero cells adapted Bangladeshi strain of peste des petits ruminants virus was studied in Vero cells to determine maximum virus yield. One-step growth curve was formulated after determining virus in both supernatant (CFV) and cell lysate (CAV) at different time categories by microtitre plate titration in Vero cells and the viral presence was confirmed by real-time RT-PCR. The virus was first detected in both the supernatants and cell pellets at 12 hpi. The virus titre reached its plateau at 72 hpi. Maximum virus titre of CAV was 6.2 log10 TCID50/ml and that of CFV was 5.2 log10 TCID50/ml at 72 hpi. After that, the titer gradually declined, but maintained at 4.5 log10 TCID50/ml in case of CAV and 4.2 log10 TCID50/ml in case of CFV at 96 hpi. It was concluded that the optimum time point for harvesting Vero cell culture is 72 hpi.

Sequential haematological and serum biochemical changes in Black Bengal goats infected with a local isolate of peste des petits ruminants virus from Bangladesh.

BACKGROUND: Knowledge of sequential changes in haematobiochemical parameters of infected animals helps in the formulation of appropriate supportive therapy. OBJECTIVE: We investigated the sequential haematological and biochemical changes in peste des petits ruminants (PPR)-infected Black Bengal goats. METHODS: Goats were either infected with PPR virus (PPRV; n = 8) or sham infected with sterile phosphate-buffered saline (n = 4) via the intranasal route. Blood and sera were collected from both groups at different days post-infection (dpi) and analysed. Goats were sacrificed at different dpi and the amount of PPRV RNA in different tissues was quantified by real-time RT-PCR. RESULTS: The PPRV-infected goats showed mild depression and scanty nasal secretions starting at 4 dpi which became severe with high fever (106°F), dyspnoea, stomatitis, profuse orinasal discharge and diarrhoea at 9-13 dpi. PPRV RNA was detected in different tissues of infected goats. Severe lymphocytic leukopenia (at 18 dpi) was observed in infected goats. Total protein and albumin decreased in infected goats starting at 10 dpi. An elevated level of enzymes (alkaline phosphatase, creatine kinase, aspartate transaminase and alanine transaminase) and metabolites (blood urea nitrogen and urea B) were found in infected goats starting at 7-10 dpi, suggesting damages in the liver and kidneys. PPR-infected goats showed elevated sodium and chloride ions starting at 7 dpi. The majority of infected goats were seroconverted by 14 dpi. CONCLUSIONS: Anti-diarrheal agents, aqua solutions and other medicine to support liver and kidney functions could be considered as supportive therapy against PPRV infection.

Detection of peste des petits ruminants virus in pneumonic lungs from apparently healthy sheep and goats slaughtered at Al-Hasaheisa slaughterhouse, Gezira state, central Sudan.

The study aimed to investigate the presence of peste des petits ruminants (PPR) in pneumonic lung tissues from clinically apparently healthy sheep and goats and further demonstrating its prevalence in Gezira state, central Sudan. During March 2019, 99 pneumonic lung samples were collected from apparently healthy sheep (80) and goats (19) from Al-Hasaheisa slaughterhouse located in Al-Hasaheisa locality, Gezira state. Using the haemagglutination (HA) test for the detection of peste des petits ruminants virus (PPRV) antigen, an overall antigenic prevalence of 86.9% was demonstrated in sheep and goats lung tissue homogenate. Of note, the prevalence of PPRV is higher in goats (100%) compared to sheep (83.7%). In this study, the reported increasing prevalence of PPR in central Sudan might be because of insufficient vaccination of animals. The findings of the present study indicated the widespread of PPR amongst sheep and goats in Al-Hasaheisa, Gezira state. Detection of PPRV antigen in the pneumonic lung samples is an indication of exposure of these animals to PPRV or presence of PPR viral infection and demonstrates the role of PPR as the cause of pneumonia in small ruminants. In fact, the circulation of the virus in clinically apparently healthy animals poses a threat for other in-contact susceptible animals and could play a significant role in the spread of the disease.