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The type I interferons (IFNs) are a group of key cytokines of the vertebrate innate immune system that induce an antiviral state in uninfected cells. Experimental in-vitro and in-vivo data have proven the fundamental role these cytokines possess in the protective response to a wide variety of pathogens, including herpesviruses. In a clinical setting, IFNs have been an important treatment in humans for several decades and increasing evidence demonstrates their potential in controlling viral haemorrhagic fevers when administered early in disease. In juvenile Asian elephants, elephant endotheliotropic herpesvirus haemorrhagic disease (EEHV-HD) often proves fatal when an effective adaptive immune response cannot be mounted in time, suggesting that an enhancement of the innate immune response could provide protection. This study sequenced six members of the Asian elephant type I IFNs, most closely related to sequences from the African elephant and Florida manatee. Subsequently, recombinant Asian elephant IFNα and IFNβ proteins were expressed and assessed for bioactivity in-vitro , relative to recombinant human IFNs, using a novel infection model incorporating primary Asian elephant fibroblasts and bovine alphaherpesvirus 1 (BoHV-1) as a surrogate for EEHV. In a dose-dependent manner, both Asian elephant IFNs and human IFNα2a protected cells from BoHV-1 infection in this proof-of-concept study, even if applied up to 24 hours post-infection in-vitro .

The immune system of Asian elephants (Elephas maximus) is poorly studied, compared to that of livestock, rodents or humans. The innate immune response has become a focus of interest in relation to Elephant endotheliotropic herpesviruses (EEHVs). EEHVs cause a fatal hemorrhagic disease (EEHV-HD) and are a significant threat to captive Asian elephant populations worldwide. Similar to other herpesvirus infections, nearly all animals become infected, but only some develop disease. As progression to EEHV-HD is often acute, a robust innate immune response is crucial to control EEHV infections. This is invariably true of the host in the first instance, but it can also potentially be modulated by intervention strategies. Here, two immunostimulant veterinary medicinal products, authorized for use in domestic species, were tested for their ability to induce innate anti-viral immune responses in Asian elephant blood cells. Sequence data were obtained for a range of previously unidentified Asian elephant immune genes, including C-X-C motif chemokine ligand 10 (CXCL10), interferon stimulated gene 15 (ISG15) and myxovirus GTPase 1 (Mx1), and were employed in the design of species-specific qPCR assays. These assays were subsequently used in analyses to determine fold changes in gene expression over a period of 24 hours. This study demonstrates that both immunostimulant medications are capable of inducing significant innate anti-viral immune responses which suggests that both could be beneficial in controlling EEHV infections in Asian elephants.

We report fatal West Nile virus (WNV) infection in a 7-year-old mare returning to the United Kingdom from Spain. Case timeline and clustering of virus sequence with recent WNV isolates suggest that transmission occurred in Andalusía, Spain. Our findings highlight the importance of vaccination for horses traveling to WNV-endemic regions.

Bovine Pestiviruses A and B, formerly known as bovine viral diarrhoea viruses (BVDV)-1 and 2, respectively, are important pathogens of cattle worldwide, responsible for significant economic losses. Bovine viral diarrhoea control programmes are in effect in several high-income countries but less so in low- and middle-income countries where bovine pestiviruses are not considered in disease control programmes. However, bovine pestiviruses are genetically and antigenically diverse, which affects the efficiency of the control programmes. The emergence of atypical ruminant pestiviruses (Pestivirus H or BVDV-3) from various parts of the world and the detection of Pestivirus D (border disease virus) in cattle highlights the challenge that pestiviruses continue to pose to control measures including the development of vaccines with improved cross-protective potential and enhanced diagnostics. This review examines the effect of bovine pestivirus diversity and emergence of atypical pestiviruses in disease control by vaccination and diagnosis.

Using the commercially available PEPperCHIP® microarray platform, a peptide microarray was developed to identify immunodominant epitopes for the detection of antibodies against Equine arteritis virus (EAV). For this purpose, the whole EAV Bucyrus sequence was used to design a total of 1250 peptides that were synthesized and spotted onto a microarray slide. A panel of 28 serum samples representing a selection of EAV strains was tested using the microarray. Of the 1250 peptides, 97 peptides (7.76%) showed reactivity with the EAV-positive samples. No single peptide was detected by all the positive serum samples. Seven peptides repeatedly showed reactivity above the cut-off and were considered to have diagnostic potential. Five of these peptides were within the immunodominant GP5 protein and two were within the replicase polyprotein regions NSP2 and NSP10, located in ORF1. The diagnostic sensitivity of the seven peptides selected was low, ranging from 5% to 55%; however, the combined diagnostic sensitivity and specificity of the seven peptides was 90% and 100%, respectively. This data demonstrate that multiple peptide sequences would be required to design a comprehensive serological test to cover the diversity of the EAV strains and the individual immune responses of horses.

The sudden mortality of African elephants ( Loxodonta africana ) in Botswana and Zimbabwe in 2020 provoked considerable public interest and speculation. Poaching and malicious poisoning were excluded early on in the investigation. Other potential causes included environmental intoxication, infectious diseases, and increased habitat stress due to ongoing drought. Here we show evidence of the mortalities in Zimbabwe as fatal septicaemia associated with Bisgaard taxon 45, an unnamed close relative of Pasteurella multocida . We analyse elephant carcasses and environmental samples, and fail to find evidence of cyanobacterial or other intoxication. Post-mortem and histological findings suggest a bacterial septicaemia similar to haemorrhagic septicaemia caused by P. multocida . Biochemical tests and 16S rDNA analysis of six samples and genomic analysis of one sample confirm the presence of Bisgaard taxon 45. The genome sequence contains many of the canonical P. multocida virulence factors associated with a range of human and animal diseases, including the pmHAS gene for hyaluronidase associated with bovine haemorrhagic septicaemia. Our results demonstrate that Bisgaard taxon 45 is associated with a generalised, lethal infection and that African elephants are susceptible to opportunistically pathogenic Pasteurella species. This represents an important conservation concern for elephants in the largest remaining metapopulation of this endangered species. A series of unexplained elephant mortalities occurred in northwest Zimbabwe in 2020. Here the authors show that six elephants died of bacterial septicaemia associated with a little-reported Pasteurella species.

We report the results of the world’s first trial of a vaccine against elephant endotheliotropic herpesvirus (EEHV) in elephants. EEHV-induced haemorrhagic disease is a major threat to juvenile Asian elephants. A vaccine preventing severe disease and death would support conservation efforts for this endangered species. We developed a heterologous, recombinant modified vaccinia virus Ankara prime and adjuvanted protein boost vaccine, containing regulatory protein EE2 and major capsid protein. Vaccine design targeted Th1 and cytotoxic T cell responses, crucial for herpesvirus immunity. In a proof-of-concept trial, safety and immunogenicity were tested in adult elephants. A modified interferon-γ release (IFNG) point-of-care vaccine-specific whole blood assay was established to avoid sample transport-related loss of immune readouts and determine T cell responses by RT-qPCR first. Subsequently, RNA sequencing was utilised to investigate transcriptomic changes post-vaccination. No adverse reactions were observed following heterologous vaccination. IFNG responses to candidate antigens were detected against the pre-existing latent immunity in adult elephants. Over-representation analysis revealed induction of T cell-associated pathways. Thus, we show that the vaccine has a favourable safety profile and stimulates EEHV-specific T cell-biased immune responses, warranting further evaluation. Elephant endotheliotropic herpesvirus (EEHV) haemorrhagic disease is a major threat for juvenile Asian elephants. This study reports a proof-of-concept trial that evaluates the safety and immunogenicity of a vaccine against EEHV.

African swine fever virus (ASFV) causes a lethal, haemorrhagic disease in domestic swine that threatens pig production across the globe. Unlike domestic pigs, warthogs, which are wildlife hosts of the virus, do not succumb to the lethal effects of infection. There are three amino acid differences between the sequence of the warthog and domestic pig RELA protein; a subunit of the NF-κB transcription factor that plays a key role in regulating the immune response to infections. Domestic pigs with all 3 or 2 of the amino acids from the warthog RELA orthologue have been generated by gene editing. To assess if these variations confer resilience to ASF we established an intranasal challenge model with a moderately virulent ASFV. No difference in clinical, virological or pathological parameters were observed in domestic pigs with the 2 amino acid substitution. Domestic pigs with all 3 amino acids found in warthog RELA were not resilient to ASF but a delay in onset of clinical signs and less viral DNA in blood samples and nasal secretions was observed in some animals. Inclusion of these and additional warthog genetic traits into domestic pigs may be one way to assist in combating the devastating impact of ASFV.

Equine viral arteritis is an infectious disease of equids caused by equine arteritis virus (EAV), an RNA virus of the family Arteriviridae. Dendritic cells (DC) are important modulators of the immune response with the ability to present antigen to naïve T cells and can be generated in vitro from monocytes (MoDC). DC are important targets for many viruses and this interaction is crucial for the establishment—or rather not—of an anti-viral immunity. Little is known of the effect EAV has on host immune cells, particularly DC. To study the interaction of eqDC with EAV in vitro, an optimized eqMoDC system was used, which was established in a previous study. MoDC were infected with strains of different genotypes and pathogenicity. Virus replication was determined through titration and qPCR. The effect of the virus on morphology, phenotype and function of cells was assessed using light microscopy, flow cytometry and in vitro assays. This study confirms that EAV replicates in monocytes and MoDC. The replication was most efficient in mature MoDC, but variable between strains. Only the virulent strain caused a significant down-regulation of certain proteins such as CD14 and CD163 on monocytes and of CD83 on mature MoDC. Functional studies conducted after infection showed that EAV inhibited the endocytic and phagocytic capacity of Mo and mature MoDC with minimal effect on immature MoDC. Infected MoDC showed a reduced ability to stimulate T cells. Ultimately, EAV replication resulted in an apoptosis-mediated cell death. Thus, EAV evades the host anti-viral immunity both by inhibition of antigen presentation early after infection and through killing infected DC during replication.

Since the reintroduction of African swine fever virus (ASFV) in Europe in 2007 and its subsequent spread to Asia, wild boar has played a crucial role in maintaining and disseminating the virus. There are significant gaps in the knowledge regarding infection dynamics and disease pathogenesis in domestic pigs and wild boar, particularly at the early infection stage. We aimed to compare domestic pigs and wild boar infected intranasally to mimic natural infection with one of the original highly virulent genotype II ASFV isolates (Armenia 2007). The study involved euthanising three domestic pigs and three wild boar on days 1, 2, 3, and 5 post-infection, while four domestic pigs and four wild boar were monitored until they reached a humane endpoint. The parameters assessed included clinical signs, macroscopic lesions, viremia levels, tissue viral load, and virus shedding in nasal and rectal swabs from day 1 post-infection. Compared with domestic pigs, wild boar were more susceptible to ASFV, with a shorter incubation period and earlier onset of clinical signs. While wild boar reached a humane endpoint earlier than domestic pigs did, the macroscopic lesions were comparatively less severe. In addition, wild boar had earlier viremia, and the virus was also detected earlier in tissues. The medial retropharyngeal lymph nodes were identified as key portals for ASFV infection in both subspecies. No viral genome was detected in nasal or rectal swabs until shortly before reaching the humane endpoint in both domestic pigs and wild boar, suggesting limited virus shedding in acute infections.