Explore the vast range of titles available.

Background The present report describes a case of pseudocowpox virus (PCPV) infection in a seven-year-old female bison euthanized due to a history of declining condition and sores on the vulva and udder. Case presentation External examination revealed multifocal, raised, keratinized plaques (0.5–2 cm) covering the skin of the ventral surface of the tail, perineum, caudoventral abdomen, udder, both inguinal recesses, and the medial aspects of both thighs. No significant gross lesions were present in the reminder of the tissues examined. Histopathological examination of the affected skin showed moderate epidermal hyperplasia with rete pegs, marked parakeratotic hyperkeratosis with crusts of degenerate neutrophils and cell debris, and few epithelial cells undergoing ballooning degeneration with occasional eosinophilic intracytoplasmic inclusion bodies (3–5 μm Bollinger body). Negative staining electron microscopy from skin revealed typical Parapoxvirus (PPV) particles, which were also confirmed by real-time PCR (Ct =18.6). Metagenomic analysis of the skin samples revealed only poxviruses. The bison parapox B2L envelope gene clustered with other parapox sequences identified from ruminants. Conclusions This is the first report of PCPV virus infection in an American bison. Identification of novel susceptible hosts of parapox viruses sheds light on the viral evolution and highlights the importance of potential economic impact of this disease to the bison industry.

Pigs with severe combined immunodeficiency (SCID) are an emerging biomedical animal model. Swine are anatomically and physiologically more similar to humans than mice, making them an invaluable tool for preclinical regenerative medicine and cancer research. One essential step in further developing this model is the immunological humanization of SCID pigs. In this work we have generated T B NK SCID pigs through site directed CRISPR/Cas9 mutagenesis of within a naturally occurring genetic background. We confirmed pigs lacked T, B, and NK cells in both peripheral blood and lymphoid tissues. Additionally, we successfully performed a bone marrow transplant on one male SCID pig with bone marrow from a complete swine leukocyte antigen (SLA) matched donor without conditioning to reconstitute porcine T and NK cells. Next, we performed injections of cultured human CD34 selected cord blood cells into the fetal SCID pigs. At birth, human CD45 CD3ε cells were detected in cord and peripheral blood of injected SCID piglets. Human leukocytes were also detected within the bone marrow, spleen, liver, thymus, and mesenteric lymph nodes of these animals. Taken together, we describe critical steps forwards the development of an immunologically humanized SCID pig model.

Severe combined immunodeficiency (SCID) is described as the lack of functional T and B cells. In some cases, mutant genes encoding proteins involved in the process of VDJ recombination retain partial activity and are classified as hypomorphs. Hypomorphic activity in the products from these genes can function in the development of T and B cells and is referred to as a leaky phenotype in patients and animals diagnosed with SCID. We previously described two natural, single nucleotide variants in ( ) in a line of Yorkshire pigs that resulted in SCID. One allele contains a splice site mutation within intron 8 of the gene ( ), while the other mutation is within exon 10 that results in a premature stop codon ( ). While initially characterized as SCID and lacking normal levels of circulating lymphoid cells, low levels of CD3ε cells can be detected in most SCID animals. Upon further assessment, we found that , and SCID pigs had abnormally small populations of CD3ε cells, but not CD79α cells, in circulation and lymph nodes. Newborn pigs (0 days of age) had CD3ε cells within lymph nodes prior to any environmental exposure. CD3ε cells in SCID pigs appeared to have a skewed CD4α CD8α CD8β T helper memory phenotype. Additionally, in some pigs, rearranged VDJ joints were detected in lymph node cells as probed by PCR amplification of TCRδ V5 and J1 genomic loci, as well as TCRβ V20 and J1.1, providing molecular evidence of residual Artemis activity. We additionally confirmed that TCRα and TCRδ constant region transcripts were expressed in the thymic and lymph node tissues of SCID pigs; although the expression pattern was abnormal compared to carrier animals. The leaky phenotype is important to characterize, as SCID pigs are an important tool for biomedical research and this additional phenotype may need to be considered. The pig model also provides a relevant model for hypomorphic human SCID patients.

•Chimeric bat influenza viruses as vaccines show no reassortment with classical influenza viruses.•Novel vaccines reduce virus replication and pathology of pigs infected with a heterologous virus.•Novel vaccines reduce virus nasal shedding in immunized and challenged pigs.•Novel vaccines induce robust mucosal and T-cell immune responses in pigs without VAERD.•Bat influenza vectored vaccines are effective and safe without VAERD and reassortment. Swine influenza is an important disease for the swine industry. Currently used whole inactivated virus (WIV) vaccines can induce vaccine-associated enhanced respiratory disease (VAERD) in pigs when the vaccine strains mismatch with the infected viruses. Live attenuated influenza virus vaccine (LAIV) is effective to protect pigs against homologous and heterologous swine influenza virus infections without inducing VAERD but has safety concerns due to potential reassortment with circulating viruses. Herein, we used a chimeric bat influenza Bat09:mH3mN2 virus, which contains both surface HA and NA gene open reading frames of the A/swine/Texas/4199–2/1998 (H3N2) and six internal genes from the novel bat H17N10 virus, to develop modified live-attenuated viruses (MLVs) as vaccine candidates which cannot reassort with canonical influenza A viruses by co-infection. Two attenuated MLV vaccine candidates including the virus that expresses a truncated NS1 (Bat09:mH3mN2-NS1-128, MLV1) or expresses both a truncated NS1 and the swine IL-18 (Bat09:mH3mN2-NS1-128-IL-18, MLV2) were generated and evaluated in pigs against a heterologous H3N2 virus using the WIV vaccine as a control. Compared to the WIV vaccine, both MLV vaccines were able to reduce lesions and virus replication in lungs and limit nasal virus shedding without VAERD, also induced significantly higher levels of mucosal IgA response in lungs and significantly increased numbers of antigen-specific IFN-γ secreting cells against the challenge virus. However, no significant difference was observed in efficacy between the MLV1 and MLV2. These results indicate that bat influenza vectored MLV vaccines can be used as a safe live vaccine to prevent swine influenza.

Abstract Swine influenza is an important disease for the swine industry. Currently used whole inactivated virus (WIV) vaccines can induce vaccine-associated enhanced respiratory disease (VAERD) in pigs when the vaccine strains mismatch with the infected viruses. Live attenuated influenza virus vaccine (LAIV) is effective to protect pigs against homologous and heterologous swine influenza virus infections without inducing VAERD, but has safety concerns due to potential reassortment with circulating viruses. Herein, we used a chimeric bat influenza Bat09:mH3mN2 virus, which contains both surface HA and NA gene open reading frames of the A/swine/Texas/4199-2/1998 (H3N2) and six internal genes from the novel bat H17N10 virus, to develop modified live-attenuated viruses (MLVs) as vaccine candidates which cannot reassort with canonical influenza A viruses by co-infection. Two attenuated MLV vaccine candidates including the virus that expresses a truncated NS1 (Bat09:mH3mN2-NS1-128, MLV1) or expresses both a truncated NS1 and the swine IL-18 (Bat09:mH3mN2-NS1-128-IL-18, MLV2) were generated and evaluated in pigs against a heterologous H3N2 virus using the WIV vaccineb as a control. Compared to the WIV vaccine, both MLV vaccines were able to reduce lesions and virus replication in lungs and limit nasal virus shedding without VAERD, also induced significantly higher levels of mucosal IgA response in lungs and significantly increased numbers of antigen-specific IFN-γ secreting cells against the challenge virus. However, no significant difference was observed in efficacy between the MLV1 and MLV2. These results indicate that bat influenza vectored MLV vaccines can be used as a safe live vaccine to prevent swine influenza. Competing Interest Statement Wenjun Ma and Jingjiao Ma have a patent entitled: Modified bat influenza viruses and their uses at Kansas State University.

Pigs with severe combined immunodeficiency (SCID) are an emerging biomedical animal model. Swine are anatomically and physiologically more similar to humans than mice, making them an invaluable tool for preclinical regenerative medicine and cancer research. One essential step in further developing this model is the immunological humanization of SCID pigs. In this work we have generated T- B- NK- SCID pigs through site directed CRISPR/Cas9 mutagenesis of IL2RG within a naturally occurring DCLRE1C (Artemis)-/- genetic background. We confirmed Art-/- IL2RG-/Y pigs lacked T, B, and NK cells in both peripheral blood and lymphoid tissues. Additionally, we and successfully performed a bone marrow transplant on one Art-/- IL2RG-/Y male SCID pig with a bone marrow from a complete swine leukocyte antigen (SLA) matched donor without conditioning to reconstitute porcine T and NK cells. Next, we performed in utero injections of cultured human CD34+ selected cord blood cells into the fetal Art-/- IL2RG-/Y SCID pigs. At birth, human CD45+ CD3ε+ cells were detected in peripheral blood of in utero injected SCID piglets. Human leukocytes were also detected within the bone marrow, spleen, liver, thymus, and mesenteric lymph nodes of these animals. Taken together, we describe critical steps forwards the development of an immunologically humanized SCID pig model.

The authors would like to thank Jason Dowell for assistance with surrogates for embryo transfer. We would like to thank Food for the 21st Century at the University of Missouri and the Intramural Research Program of NIH, NCI, Center for Cancer Research for providing funding for this project.

A 20-year-old, female African grey parrot (Psittacus erithacus erithacus) was examined because of ataxia and weakness. Radiographs were unremarkable, and results of a complete blood cell count revealed leukocytosis and heterophilia. Because of poor response to therapy with meloxicam, doxycycline, and enrofloxacin; deteriorating condition; and poor prognosis, the parrot was euthanatized. Postmortem examination revealed 2 dark red nodules in the liver. No grossly visible mass was observed in the syrinx. Histologic examination of the liver and syrinx revealed similar foci of round, oval, and polygonal cells exhibiting severe pleomorphism, with poorly demarcated cytoplasmic borders and moderate amounts of eosinophilic cytoplasm containing brown to black granules (melanin). The mitotic index was 15. The presence of melanin pigment is consistent with a diagnosis of melanoma at both sites. The multifocal distribution and intravascular invasion indicate metastasis; however, the site of origin was unknown. To our knowledge, this is the first recorded case of melanoma in an avian syrinx.

Severe combined immunodeficiency (SCID) is a rare group of inherited disorders characterized by defects in both humoral and cellular immune functions. Naturally occurring SCID has been first described in humans in the 1960s and subsequently identified in horses, mice, and dogs, but never before in pigs. Affected animals are characterized by having loss of functional B and T lymphocytes, and in some cases natural killer (NK) cells, but normal numbers of monocytes, granulocytes, and megakaryocytes. As a result, affected animals fail to produce antibodies and succumb to common disease pathogens after circulating maternal antibodies decay. SCID models are extremely valuable for the understanding of molecular mechanisms of immunological processes during viral and bacterial diseases, cancer, and autoimmunity. SCID mice are widely used as the current model; however, the relevance of the murine SCID model to human and veterinary immune research is limited and there is an increasing need for a more representative model of SCID is imperative. We describe the gross, microscopic, and immunophenotypic characteristics of a line of Yorkshire pigs having naturally occurring SCID. Affected pigs lack T and B lymphocytes, but display circulating NK cells, fail to produce antibodies to viral infection, and lack cell-mediated response to tumor xenotransplants. We also describe response of SCID pigs to porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV is the most devastating virus in swine industry, causing losses of billions of dollars annually. Understanding the immunopathogenesis of the disease is imperative in order to develop strategies to combat this devastating virus. PRRSV infected-SCID pigs failed to develop lesions of PRRSV infection, demonstrating the significant role of the adaptive immunity to PRRSV infection. Finally, we describe the preliminary results of the adoptive transfer of purified CD3+ T lymphocytes to SCID pigs from SLA-II matched wild-type littermates, with the objective of establishing a porcine model for the study of T cell immunopathogenesis with viral diseases.