Whole-Genome-Sequence-Based Evolutionary Analyses of HoBi-like Pestiviruses Reveal Insights into Their Origin and Evolutionary History.

HoBi-like pestivirus (HoBiPeV), classified under Pestivirus H species, is an emerging cattle pathogen of high economic impact. However, the origin and evolution of HoBiPeV are not very clear due to a lack of full genomic sequences from diverse clades. This study aimed to determine full-genome sequences of HoBiPeV strains of three novel clades (c, d and e) and perform full-genome-based genetic and evolutionary analyses. Bayesian phylogenetic analyses herein confirmed the existence and independent evolution of four main HoBiPeV clades (a, c, d and e) globally, with genetic divergence ranging from 13.0% to 18.2%. Our Bayesian molecular clock estimates revealed that HoBiPeV most likely originated in India, with a dated tMRCA of 1938 (1762-2000), evidencing a more recent origin of HoBiPeV. The evolution rate of HoBiPeV was estimated to be 2.133 × 10-3 subs/site/year at full-genome level but varied widely among individual genes. Selection pressure analyses identified most of the positively selected sites in E2. Additionally, 21.8% of the ORF codon sites were found under strong episodic diversifying selection, providing first evidence of negative selection in HoBiPeV evolution. No recombination event was evident for HoBiPeV-c, d and e strains. These findings provide new insights into HoBiPeV origin and evolutionary history for better understanding the epidemiology and host-pathogen interactions and stimulate vaccine research.

Molecular characterization of peste-des-petits ruminants virus (PPRV) isolated from an outbreak in the Indo-Bangladesh border of Tripura state of North-East India.

Peste-des-petits- ruminants (PPR) is a highly contagious and devastating disease of goats and sheep. Although India is endemic for PPR, Tripura, a state in North East India has never been reported confirmed PPR outbreaks. Recently, an outbreak of PPR occurred in non-descript goats at the Sabroom town of Tripura state in North-East India in June, 2013. The causative agent, PPR virus (PPRV) was confirmed by sandwich ELISA, virus isolation and N gene based RT-PCR and sequencing. The sequence and phylogenetic analysis confirmed the involvement of lineage IV PPR virus in the outbreak. The outbreak viruses from Tripura state were clustered mainly with circulating viruses from Bangladesh, India, China, Pakistan, Tajikistan, Dubai and Kurdistan. However, the nucleotide sequence homology ranged from 99.2 to 99.6% with the PPR strains circulating in Bangladesh during 2011 and 2012 whereas 95.5-98% homology has been observed with the viruses from India and other countries. These findings suggest the transboundary circulation of PPR virus between India and Bangladesh border, which warrant immediate vaccination across the international border to create an immune belt.

Cytokines expression profile and kinetics of Peste des petits ruminants virus antigen and antibody in infected and vaccinated goats.

The present study deals with the co-ordination of cytokine (IL-4 and IFN-γ) expression and kinetics of peste des petits ruminants (PPR) virus antigen and antibody in PPRV infected and vaccinated goats. The infected animals exhibited mixed cytokine (both T(H)1 and T(H)2) responses in the initial phase of the disease. The infected and dead goats had increased IFN-γ response before their death; while IL-4 remained at the base level. The cytokine expression in recovered animals was almost similar to that of vaccinated ones, where a unique biphasic response of IL-4 expression was observed with an up-regulation of IFN-γ on 7(th) days post vaccination (dpv). Analysis of PPR virus antigen and antibody kinetics in different components of blood from infected and vaccinated animals revealed that the PPR virus antigen load was highest in plasma followed by serum and blood of the infected animals, whereas vaccinated animals showed only marginal positivity on 9(th) dpv. The antibody titer was high in serum followed by plasma and blood in both vaccinated and infected animals. Therefore, it is inferred that the presence of antigen and antibody were significant with the expression of cytokine, and that a decreased response of IL-4 was noticed during intermediate phase of the disease i.e., 7 to 12(th) days post infection (dpi). This indicates the ability to mount a functional T(H)2 response after 14(th) dpi could be a critical determinant in deciding the survival of the PPR infected animal.

Effect of immunosuppression on pathogenesis of peste des petits ruminants (PPR) virus infection in goats.

In this study an attempt to address the effects of immunosuppression on pathogenesis of peste des petits ruminants (PPR) virus infection was undertaken. Cyclophosphamide and dexamethasone were used to immunosuppress the animals. The drug treated animals exhibited severe leukopaenia and lymphopaenia; one of the indicators of immunosuppression. Experimental peste des petits ruminants virus (PPRV) infection was then given to both drug-induced immunosuppressed and non-immunosuppressed goats and observed their effects. Findings indicated that, the immunosuppressed goats had a short period of viremia, more extensive and severe disease advancement and higher mortality rate than the non-immunosuppressed goats. PPRV antigen distribution in both ante-mortem and post-mortem materials was extensive and diffused in immunosuppressed animals than that of non-immunosuppressed. Some of the atypical organ(s)/tissues like liver, kidney, heart etc showed more antigen load than non-immunosuppressed group. Histopathological and immunohistochemical studies of tissues from the two groups showed that pathological changes in the non-immunosuppressed animals were confined only to gastrointestinal tract, whereas in the immunosuppressed animals histopathological changes and PPRV antigen distribution were more extensive and diffused. The present study indicated that immunosuppression increased the extent and severity of the pathological lesions associated with peste des petits ruminants virus infection.