Dromedaries are an important livestock, used as beasts of burden and for meat and milk production. However, they can act as an intermediate source or vector for transmitting zoonotic viruses to humans, such as the Middle East respiratory syndrome coronavirus (MERS-CoV) or Crimean-Congo hemorrhagic fever virus (CCHFV). After several outbreaks of CCHFV in the Arabian Peninsula, recent studies have demonstrated that CCHFV is endemic in dromedaries and camel ticks in the United Arab Emirates (UAE). There is no apparent disease in dromedaries after the bite of infected ticks; in contrast, fever, myalgia, lymphadenopathy, and petechial hemorrhaging are common symptoms in humans, with a case fatality ratio of up to 40%. We used the in-solution hybridization capture of 100 annotated immune genes to genotype 121 dromedaries from the UAE tested for seropositivity to CCHFV. Through univariate linear regression analysis, we identified two candidate genes belonging to the innate immune system: FCAR and CLEC2B. These genes have important functions in the host defense against viral infections and in stimulating natural killer cells, respectively. This study opens doors for future research into immune defense mechanisms in an enzootic host against an important zoonotic disease.

• Klíčová slova
• Camelus dromedarius, Old World camel, in-solution hybridization capture, tick, vector-borne infection, zoonosis,
• MeSH
• genetická predispozice k nemoci genetika   MeSH
• genotyp MeSH
• hemoragická horečka krymská genetika   imunologie   virologie   MeSH
• infestace klíšťaty imunologie   parazitologie   MeSH
• klíšťata imunologie   fyziologie   virologie   MeSH
• koronavirové infekce genetika   imunologie   virologie   MeSH
• kuřecí embryo MeSH
• lidé MeSH
• odolnost vůči nemocem genetika   imunologie   MeSH
• přirozená imunita genetika   imunologie   MeSH
• rizikové faktory MeSH
• velbloudi genetika   imunologie   virologie   MeSH
• virus krymsko-konžské hemoragické horečky imunologie   fyziologie   MeSH
• zoonózy genetika   imunologie   virologie   MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Spojené arabské emiráty MeSH

Targeted cancer immunotherapy is a promising tool for restoring immune surveillance and eradicating cancer cells. Hydrophilic polymers modified with coiled coil peptide tags can be used as universal carriers designed for cell-specific delivery of such biologically active proteins. Here, we describe the preparation of pHPMA-based copolymer conjugated with immunologically active protein B7-H6 via complementary coiled coil VAALEKE (peptide E) and VAALKEK (peptide K) sequences. Receptor B7-H6 was described as a binding partner of NKp30, and its expression has been proven for various tumor cell lines. The binding of B7-H6 to NKp30 activates NK cells and results in Fas ligand or granzyme-mediated apoptosis of target tumor cells. In this work, we optimized the expression of coiled coil tagged B7-H6, its ability to bind activating receptor NKp30 has been confirmed by isothermal titration calorimetry, and the binding stoichiometry of prepared chimeric biopolymer has been characterized by analytical ultracentrifugation. Furthermore, this coiled coil B7-H6-loaded polymer conjugate activates NK cells in vitro and, in combination with coiled coil scFv, enables their targeting towards a model tumor cell line. Prepared chimeric biopolymer represents a promising precursor for targeted cancer immunotherapy by activating the cytotoxic activity of natural killer cells.

• Klíčová slova
• B7-H6, HPMA polymer, NK cell, NKp30, coiled coil, immunotherapy,
• Publikační typ
• časopisecké články MeSH

The Feline coronavirus (FCoV) can cause a fatal disease, the Feline Infectious Peritonitis. Persistent shedders represent the most important source of infection. The role of the host in FCoV fecal shedding is unknown. The objective of this study was to develop gene markers and to test their associations with FCoV shedding patterns. Fecal samples were taken from 57 cats of 12 breeds on the day 0 and after 2, 4 and 12 months. Variation from persistent and/or high-intensity shedding to no shedding was observed. Thirteen immunity-related genes were selected as functional and positional/functional candidates. Positional candidates were selected in a candidate region detected by a GWAS analysis. Tens to hundreds of single nucleotide polymorphisms (SNPs) per gene were identified using next generation sequencing. Associations with different phenotypes were assessed by chi-square and Fisher's exact tests. SNPs of one functional and one positional candidate (NCR1 and SLX4IP, respectively) and haplotypes of four genes (SNX5, NCR2, SLX4IP, NCR1) were associated with FCoV shedding at pcorected < 0.01. Highly significant associations were observed for extreme phenotypes (persistent/high-intensity shedders and non-shedders) suggesting that there are two major phenotypes associated with different genotypes, highly susceptible cats permanently shedding high amounts of viral particles and resistant non-shedders.

• Klíčová slova
• association study, fecal shedding patterns, feline enteric coronavirus, genetic susceptibility, immunity-related candidate genes, polymerase-chain reaction,
• Publikační typ
• časopisecké články MeSH

Due to production of special homodimeric heavy chain antibodies, somatic hypermutation of their T-cell receptor genes and unusually low diversity of their major histocompatibility complex genes, camels represent an important model for immunogenetic studies. Here, we analyzed genes encoding selected natural killer cell receptors with a special focus on genes encoding receptors for major histocompatibility complex (MHC) class I ligands in the two domestic camel species, Camelus dromedarius and Camelus bactrianus. Based on the dromedary genome assembly CamDro2, we characterized the genetic contents, organization, and variability of two complex genomic regions, the leukocyte receptor complex and the natural killer complex, along with the natural cytotoxicity receptor genes NCR1, NCR2, and NCR3. The genomic organization of the natural killer complex region of camels differs from cattle, the phylogenetically most closely related species. With its minimal set of KLR genes, it resembles this complex in the domestic pig. Similarly, the leukocyte receptor complex of camels is strikingly different from its cattle counterpart. With KIR pseudogenes and few LILR genes, it seems to be simpler than in the pig. The syntenies and protein sequences of the NCR1, NCR2, and NCR3 genes in the dromedary suggest that they could be human orthologues. However, only NCR1 and NCR2 have a structure of functional genes, while NCR3 appears to be a pseudogene. High sequence similarities between the two camel species as well as with the alpaca Vicugna pacos were observed. The polymorphism in all genes analyzed seems to be generally low, similar to the rest of the camel genomes. This first report on natural killer cell receptor genes in camelids adds new data to our understanding of specificities of the camel immune system and its functions, extends our genetic knowledge of the innate immune variation in dromedaries and Bactrian camels, and contributes to studies of natural killer cell receptors evolution in mammals.

• Klíčová slova
• SNP, camelid, leukocyte receptor complex, microsatellites, natural killer complex,
• Publikační typ
• časopisecké články MeSH