Elevated VEGF Levels in Pulmonary Edema Fluid and PBMCs from Patients with Acute Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome is characterized by vascular permeability, hypoxia, and acute pulmonary edema. Vascular endothelial growth factor (VEGF) is induced by hypoxia, potently induces vascular permeability, and is associated with high-altitude-induced pulmonary edema. Hantaviruses alter the normal regulation of β3 integrins that restrict VEGF-directed permeability and hantavirus infected endothelial cells are hyperresponsive to the permeabilizing effects of VEGF. However, the role of VEGF in acute pulmonary edema observed in HPS patients remains unclear. Here we retrospectively evaluate VEGF levels in pulmonary edema fluid (PEF), plasma, sera, and PBMCs from 31 HPS patients. VEGF was elevated in HPS patients PEF compared to controls with the highest levels observed in PEF samples from a fatal HPS case. VEGF levels were highest in PBMC samples during the first five days of hospitalization and diminished during recovery. Significantly increased PEF and PBMC VEGF levels are consistent with acute pulmonary edema observed in HPS patients and HPS disease severity. We observed substantially lower VEGF levels in a severe HPS disease survivor after extracorporeal membrane oxygenation. These findings suggest the importance of patients’ VEGF levels during HPS, support the involvement of VEGF responses in HPS pathogenesis, and suggest targeting VEGF responses as a potential therapeutic approach

Validation of the 50k Illumina goat SNP chip in the South African Angora goat

Tools for the genomic evaluation of goats have generally lagged behind those for other species. However, the recent availability of the goat SNP50 consortium bead chip has marked a positive change for this small ruminant species. Polymorphic loci can differ greatly between breeds of the same species. Exclusion of fibre-producing breeds, such as the Angora goat, during the development of this genotyping array necessitates the validation of SNPs included on the chip to allow for genomic applications that would accelerate genetic progress in mohair yield and quality. Forty eight unrelated Angora goats, displaying phenotypic variation in two important price-determining traits, namely fibre diameter and fleece weight, were genotyped with the goat SNP50 consortium bead chip. Results revealed that 46 983 SNP (88.1%) of the 53 347 called SNPs were polymorphic (MAF>0.05). After quality control, 3 960 SNP were filtered from further analysis for violating Hardy-Weinberg and call-rate parameter thresholds, leaving 43 759 (82%) of the 53 347 SNPs to be validated for downstream analysis. Observed and expected heterozygosity values of 0.365 and 0.370, respectively, were obtained for polymorphic SNPs. A total of 30 357 SNPs in linkage disequilibrium (LD) were removed to obtain a set of independent markers, resulting in a final SNP density of 1 SNP/ ~226 kb. Results indicate that the goat SNP50 bead chip was informative in the Angora goats that were studied, and should be useful in examining the underlying genetic variation.http://www.sasas.co.zaam201

SNP-based genetic diversity of South African commercial dairy and fibre goat breeds

Goats (Capra aegagrus hircus) have not been a prioritized livestock species with regards to molecular research. The genetic characterization of commercial South African (SA) goat breeds should contribute to improving the management of available animal genetic resources. The aim of this study was to investigate genetic diversity within and among SA commercial goat breeds utilizing the 50k goat beadchip. 88 goats originating from four breeds (dairy: British Alpine, Saanen, Toggenburg; fibre: Angora) were genotyped with the goat SNP50 beadchip. Average MAF values ranged from 0.25 for the Angora to 0.29 for the Saanen, with 46 983 and 50 368 polymorphic SNPs obtained for the respective breeds. Observed heterozygosity values ranged from 0.365 for the Angora to 0.431 for the Toggenburg breed. Linkage disequilibrium (LD) estimation revealed average r2 values of 0.12 and 0.15 for dairy and fibre breeds, respectively. LD decay was shown to occur after a distance interval of 20-40kb and 40-60kb for dairy and Angora breeds, respectively. Principal component analysis (PCA) produced clusters corresponding to the different production types (dairy and fibre). The Angora, British Alpine and Saanen breeds showed high proportions of membership to respective inferred ancestral populations with ADMIXTURE (97%, 84% and 92%, respectively). The results obtained in this study indicated genetic uniformity within dairy and fibre goats due to productionspecific trait selection. Sufficient levels of genetic variation was, however, observed to allow genetic progress for SA commercial goat breeds pending the improved management of these goat genetic resources.UP Genomics Research Institute.http://www.elsevier.com/locate/smallrumres2017-03-31hb2016Animal and Wildlife Science

Levofloxacin Cures Experimental Pneumonic Plague in African Green Monkeys

Yersinia pestis is the causative agent of bubonic plague as well as a rare severe form known as primary pneumonic plague resulting from the inhalation of contaminated aerosols. The relative ease of aerosol preparation and high virulence makes Y. pestis a dangerous bioweapon. The current study describes the treatment of established pneumonic plague with the widely available, broad-spectrum fluoroquinolone antibiotic levofloxacin in a nonhuman primate model. African green monkeys inhaled a target dose of 100 lethal doses for 50% of animals (LD50) and were monitored for fever and vital signs by telemetry. Fever was the first sign of illness, correlating with bacteremia but preceding radiographic pneumonia, and initiated intravenous levofloxacin treatment in doses designed to mimic antibiotic levels achieved in humans. All animals treated with saline died and all animals completing 10 days of treatment survived, with resolution of high fever within 24–48 hours. We conclude that levofloxacin may be an appropriate broad-spectrum antibiotic for presumptive therapy in an aerosolized bioweapons attack and should be studied for treatment of bubonic plague

Hantavirus Pulmonary Syndrome: CD8+and CD4+Cytotoxic T Lymphocytes to Epitopes on Sin Nombre Virus Nucleocapsid Protein Isolated during Acute Illness

AbstractIn 1993 a number of cases of unexplained adult respiratory syndrome occurred in the southwestern United States. The illness was characterized by a prodrome of fever, myalgia, and other symptoms followed by the rapid onset of a capillary leak syndrome with hemoconcentration, thrombocytopenia, and pulmonary edema. Viral RNA sequences in the lungs identified a new member of the hantavirus genus, Sin Nombre virus (SNV), unique to North America. Pulmonary endothelial cells were heavily infected but were not necrotic. We speculated that this capillary leak syndrome was initiated by immune responses to the SNV-infected pulmonary endothelial cells. We isolated a CD8+cytotoxic T lymphocyte (CTL) clone directly from the blood of a patient with the acute hantavirus pulmonary syndrome (HPS) which recognizes a SNV specific epitope on the virus nucleocapsid protein (aa 234–242) that is restricted by HLA C7 and produces IFNγ but not IL-4. We identified a second CD8+CTL epitope located within another site aa 131–139 on the nucleocapsid protein, which is HLA B35 restricted, and a CD4+CTL epitope located on a third site on nucleocapsid protein aa 372–380 using lymphocytes obtained during HPS from another patient that were stimulatedin vitro.Hantavirus specific CD8+and CD4+CTL may contribute to the immunopathology and capillary leak syndrome observed in the HPS

Whole-genome SNP characterisation provides insight for sustainable use of local South African livestock populations

Local cattle and sheep populations are important for animal production and food security in South Africa. These genetic resources are well adapted to the diverse climatic conditions and hold potential to be utilized in production systems subjected to climate change. The local beef breeds are well integrated into commercial livestock production systems with access to performance recording and genetic evaluations, while local sheep breeds are mainly utilised in smallholder and communal systems. The GeneSeek® Genomic Profiler™ Bovine 150 K SNP genotyping array was used to evaluate the diversity and inbreeding status of four indigenous (Boran, Drakensberger, Nguni, Tuli), two composite (Bonsmara and Beefmaster) and two exotic (SA Hereford and Charolais) beef breeds. The Illumina® Ovine 50 K SNP BeadChip was used to investigate five indigenous (Black Head Persian, Damara, Fat tail, Namaqua Afrikaner, Pedi) and three commercial (Dorper, Dohne Merino and SA Merino) populations. Although ascertainment bias was indicated by the low MAF (the autosome-wide proportion of SNPs with MAF< 0.05 ranged from 6.18 to 9.97% for cattle, and 7.59–13.81% for sheep), moderate genomic diversity was observed (mean Ho ranged from 0.296 to 0.403 for cattle, and 0.327 to 0.367 for sheep). Slightly higher levels of ROH-based inbreeding were calculated for cattle (FROH range: 0.018–0.104), than for sheep populations (FROH range: 0.002–0.031). The abundance of short ROH fragments (mean proportion of <4Mb fragments: 0.405 for cattle, and 0.794 for sheep) indicated ancient inbreeding in both species. The eight cattle populations were categorized into indicine, taurine or Sanga subspecies based on principal component, model-based clustering and phylogenetic analyses, with high levels of admixture observed within the Drakensberger, Nguni and Tuli breeds. Within the sheep populations, a clear distinction could be seen between the dual-purpose breeds, the meat breed and the indigenous breeds. Despite directional selection practiced in the cattle breeds, genomic diversity was moderate with low inbreeding. The non-commercialized, indigenous sheep populations are more vulnerable with small effective populations. These results emphasise the value of genomic information for effective management to exploit the potential contribution of local genetic cattle and sheep resources in a changing environment.SUPPLEMENTARY MATERIAL: Image 1 : Whole-genome SNP characterisation provides insight for sustainable use of local South African livestock populations. Image 2 : Whole-genome SNP characterisation provides insight for sustainable use of local South African livestock populations. Image 3 : Whole-genome SNP characterisation provides insight for sustainable use of local South African livestock populations.Beef cattle genotypes used in the analyses were generated within the SA Beef Genomic Program funded by the Technology Innovation Agency. Sheep genotypes were provided for the study by the Grootfontein Agricultural Development Institute and the Western Cape Agricultural Trust.http://www.frontiersin.org/Geneticsam2022Animal and Wildlife Science

Genomic diversity and autozygosity within the SA Drakensberger beef cattle breed

Please read abstract in the article.The Beef Genomics Program (BGP) and the Red Meat Research and Development Trust of South Africa (RMRDT-SA) and financial assistance of the National Research Foundation (NRF).http://www.elsevier.com/locate/livsci2019-06-01hj2019Animal and Wildlife Science

Genetic diversity and population structure in South African, French and Argentinian angora goats from genome-wide SNP data

The Angora goat populations in Argentina (AR), France (FR) and South Africa (SA) have been kept geographically and genetically distinct. Due to country-specific selection and breeding strategies, there is a need to characterize the populations on a genetic level. In this study we analysed genetic variability of Angora goats from three distinct geographical regions using the standardized 50k Goat SNP Chip. A total of 104 goats (AR: 30; FR: 26; SA: 48) were genotyped. Heterozygosity values as well as inbreeding coefficients across all autosomes per population were calculated. Diversity, as measured by expected heterozygosity (HE) ranged from 0.371 in the SA population to 0.397 in the AR population. The SA goats were the only population with a positive average inbreeding coefficient value of 0.009. After merging the three datasets, standard QC and LD-pruning, 15 105 SNPs remained for further analyses. Principal component and clustering analyses were used to visualize individual relationships within and between populations. All SA Angora goats were separated from the others and formed a well-defined, unique cluster, while outliers were identified in the FR and AR breeds. Apparent admixture between the AR and FR populations was observed, while both these populations showed signs of having some common ancestry with the SA goats. LD averaged over adjacent loci within the three populations per chromosome were calculated. The highest LD values estimated across populations were observed in the shorter intervals across populations. The Ne for the Angora breed was estimated to be 149 animals ten generations ago indicating a declining trend. Results confirmed that geographic isolation and different selection strategies caused genetic distinctiveness between the populations.S1 Fig. Admixture plots for K = 2–4 showing population structure of different Angora subpopulations.The authors thank Margarita Cano (supplying Argentinean Angora DNA samples), Hector Taddeo (for historical information on the Argentinian Angora breed) and Capgenes (supplying French Angora DNA samples and historical information on the French Angora breed).The Argentinian part (MP) of the project was financially supported by Instituto Nacional de Tecnologia Agropecuaria PNBIO1131033 project. The South African researchers acknowledge the National Research Foundation (grants KIC14011761093 (CV) and TP13073024535 (EVMK)) and the University of Pretoria Genomics Research Institute (CV) for financial support.http://www.plosone.orgam2016Animal and Wildlife Science

Pedigree and genome-based patterns of homozygosity in the South African Ayrshire, Holstein, and Jersey breeds

DATA AVAILABILITY STATEMENT : The data analyzed in this study is subject to the following licenses/restrictions: Genomic data was obtained from SA Stud Book, a local service provider of genetic and genomic analyses in South Africa. The data thus belongs to third parties (SA Stud Book and Breed Societies). Requests to access these datasets should be directed to the corresponding authors.The erosion of genetic diversity limits long-term genetic gain and impedes the sustainability of livestock production. In the South African (SA) dairy industry, the major commercial dairy breeds have been applying estimated breeding values (EBVs) and/or have been participating in Multiple Across Country Evaluations (MACE). The transition to genomic estimated breeding values (GEBVs) in selection strategies requires monitoring of the genetic diversity and inbreeding of current genotyped animals, especially considering the comparatively small population sizes of global dairy breeds in SA. This study aimed to perform a homozygosity-based evaluation of the SA Ayrshire (AYR), Holstein (HST), and Jersey (JER) dairy cattle breeds. Three sources of information, namely 1) single nucleotide polymorphism (SNP) genotypes (3,199 animals genotyped for 35,572 SNPs) 2) pedigree records (7,885 AYR; 28,391 HST; 18,755 JER), and 3) identified runs of homozygosity (ROH) segments were used to quantify inbreeding related parameters. The lowest pedigree completeness was for the HST population reducing from a value of 0.990 to 0.186 for generation depths of one to six. Across all breeds, 46.7% of the detected ROH were between 4 megabase pairs (Mb) and 8 Mb in length. Two conserved homozygous haplotypes were identified in more than 70% of the JER population on Bos taurus autosome (BTA) 7. The JER breed displayed the highest level of inbreeding across all inbreeding coefficients. The mean (± standard deviation) pedigree-based inbreeding coefficient (FPED) ranged from 0.051 (±0.020) for AYR to 0.062 (±0.027) for JER, whereas SNPbased inbreeding coefficients (FSNP) ranged from 0.020 (HST) to 0.190 (JER) and ROH-based inbreeding coefficients, considering all ROH segment coverage (FROH), ranged from 0.053 (AYR) to 0.085 (JER). Within-breed Spearman correlations between pedigree-based and genome-based estimates ranged from weak (AYR: 0.132 between FPED and FROH calculated for ROH <4Mb in size) to moderate (HST: 0.584 between FPED and FSNP). Correlations strengthened between FPED and FROH as the ROH length category was considered lengthened suggesting a dependency on breed-specific pedigree depth. The genomic homozygosity-based parameters studied proved useful in investigating the current inbreeding status of reference populations genotyped to implement genomic selection in the three most prominent South African dairy cattle breeds.The SA Dairy Genomic Program funded by the Technology Innovation Agency.http://www.frontiersin.org/Geneticsam2024Animal and Wildlife SciencesSDG-02:Zero Hunge

Convalescent Pulmonary Dysfunction Following Hantavirus Pulmonary Syndrome in Panama and the United States

The objective of this study was to document persistent pulmonary symptoms and pulmonary function abnormalities in adults surviving hantavirus pulmonary syndrome (HPS). Acute infection by most hantaviruses result in mortality rates of 25–35%, while in Panama the mortality rate of 10% is contrasted by an unusually high incidence. In all types of HPS, the viral prodrome, cardiopulmonary phase due to massive pulmonary capillary leak syndrome, and spontaneous diuresis are followed by a convalescent phase with exertional dyspnea for 3–4 weeks, but the frequency of persistent symptoms is not known. In this observational study of a convenience sample, 14 survivors of HPS caused by Choclo virus infection in Panama and 9 survivors of HPS caused by Sin Nombre virus infection in New Mexico completed a questionnaire and pulmonary function tests up to 8 years after infection. In both groups, exertional dyspnea persisted for 1–2 years after acute infection in 43% (Panama) and 77% (New Mexico) of survivors surveyed. Reduction in midexpiratory flows (FEF25–75%), increased residual volume (RV), and reduced diffusion capacity (DLCO/VA) also were common in both populations; but the severity of reduced expiratory flow did not correlate with exertional dyspnea. Symptoms referable to previous hantavirus infection had resolved within 3 years of acute infection in most but not all patients in the Panama group. Temporary exertional dyspnea and reduced expiratory flow are common in early convalescence after HPS but resolves in almost all patients