Most cited article - PubMed ID 32883205
Nucleotide diversity of functionally different groups of immune response genes in Old World camels based on newly annotated and reference-guided assemblies
We identified and characterized 11 polymorphic microsatellite markers suitable for routine testing (three in the MHC class I sub-region, four in MHC class II and four in the MHC class III sub-region) of dromedaries and Bactrian camels. In total, 38 dromedaries and 33 Bactrian camels were genotyped, and interspecific differences were observed in the numbers of alleles and in allelic frequencies, as well as in the observed heterozygosity. These loci may be used as markers to study the adaptive genetic diversity of the MHC region in Old World camels.
- Keywords
- Camelus bactrianus, Camelus dromedarius, camels, genetic diversity, major histocompatibility complex, microsatellite markers,
- Publication type
- Journal Article MeSH
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.
- Keywords
- Camelus dromedarius, Old World camel, in-solution hybridization capture, tick, vector-borne infection, zoonosis,
- MeSH
- Genetic Predisposition to Disease genetics MeSH
- Genotype MeSH
- Hemorrhagic Fever, Crimean genetics immunology virology MeSH
- Tick Infestations immunology parasitology MeSH
- Ticks immunology physiology virology MeSH
- Coronavirus Infections genetics immunology virology MeSH
- Chick Embryo MeSH
- Humans MeSH
- Disease Resistance genetics immunology MeSH
- Immunity, Innate genetics immunology MeSH
- Risk Factors MeSH
- Camelus genetics immunology virology MeSH
- Hemorrhagic Fever Virus, Crimean-Congo immunology physiology MeSH
- Zoonoses genetics immunology virology MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- United Arab Emirates MeSH
The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.
- Keywords
- Old World camels, coronavirus, immune response genes, in-solution hybridization capture, zoonosis,
- MeSH
- Adaptive Immunity genetics MeSH
- Bronchi cytology physiology MeSH
- Cilia physiology MeSH
- COVID-19 genetics immunology virology MeSH
- Genetic Predisposition to Disease MeSH
- Host Microbial Interactions genetics immunology MeSH
- Coronavirus Infections genetics immunology transmission virology MeSH
- Middle East Respiratory Syndrome Coronavirus immunology isolation & purification pathogenicity MeSH
- Humans MeSH
- Communicable Diseases, Emerging genetics immunology transmission virology MeSH
- Immunity, Innate genetics MeSH
- Antibodies, Viral MeSH
- Virus Replication genetics immunology MeSH
- Respiratory Mucosa cytology physiology MeSH
- SARS-CoV-2 immunology pathogenicity MeSH
- Camelus genetics immunology virology MeSH
- Disease Reservoirs virology MeSH
- Zoonoses genetics immunology transmission virology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- United Arab Emirates MeSH
- Names of Substances
- Antibodies, Viral MeSH
Cytotoxic T cells and natural killer cells can kill target cells based on their expression and release of perforin, granulysin, and granzymes. Genes encoding these molecules have been only poorly annotated in camelids. Based on bioinformatic analyses of genomic resources, sequences corresponding to perforin, granulysin, and granzymes were identified in genomes of camelids and related ungulate species, and annotation of the corresponding genes was performed. A phylogenetic tree was constructed to study evolutionary relationships between the species analyzed. Re-sequencing of all genes in a panel of 10 dromedaries and 10 domestic Bactrian camels allowed analyzing their individual genetic polymorphisms. The data showed that all extant Old World camelids possess functional genes for two pore-forming proteins (PRF1, GNLY) and six granzymes (GZMA, GZMB, GZMH, GZMK, GZMM, and GZMO). All these genes were represented as single copies in the genome except the GZMH gene exhibiting interspecific differences in the number of loci. High protein sequence similarities with other camelid and ungulate species were observed for GZMK and GZMM. The protein variability in dromedaries and Bactrian camels was rather low, except for GNLY and chymotrypsin-like granzymes (GZMB, GZMH).
- Keywords
- NK cells, camel, cytotoxic T lymphocytes, granulysin, granzymes, perforin, ungulates,
- MeSH
- Killer Cells, Natural metabolism MeSH
- Pore Forming Cytotoxic Proteins genetics MeSH
- T-Lymphocytes, Cytotoxic metabolism MeSH
- Phylogeny MeSH
- Granzymes genetics MeSH
- Perforin genetics MeSH
- Camelidae classification genetics MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Pore Forming Cytotoxic Proteins MeSH
- Granzymes MeSH
- Perforin MeSH