Abstract
Although poultry industry has gained momentum during the last few decades, there are still various impediments like improper infrastructure, unscientific management and above all various deadly infectious diseases which incur huge economic losses on poultry industry. These diseases include viral diseases like Avian Influenza, Marek’s Disease, New Castle disease and bacterial diseases like Colibacillosis, Pasteurellosis and Salmonellosis, etc. Development of disease resistant poultry has been found successful practice over the use of drugs or vaccines for disease control. Studies involving genome wide associations to figure out certain candidate genes that are involved in disease resistance have also been carried out. Single nucleotide polymorphism studies to unveil the mechanisms underlying disease resistance in chicken show that SNPs and other candidate gene approaches play a vital role in providing disease resistance. Also, understanding the genes and biological pathways that confer genetic resistance to various infections will lead towards the development of more resistant commercial poultry flocks or improved vaccines against various diseases. This chapter shall focus on various factors involved in disease resistance in chicken that interact with the pathogen and provide resistance against the pathogen.
Keywords
- chicken
- genetics
- pathogen
- disease resistance
1. Introduction
Poultry is a principal component in the global agricultural economy by serving as one of the primary sources of proteins for humans. Worldwide egg and poultry meat production is close to 73 million tons and 100 million tons respectively [1]. Despite such an increase in the growth of poultry industry, this industry is consistently threatened by various diseases, including those caused by viral, bacterial and parasitic infections. These diseases can lead to substantial economic losses in two ways, firstly there is a reduction in the production of poultry related products, and also the input costs like labour and feed get increased. The impact of these loses in poultry industry is more worse on the livelihood of poor people in the developing countries where up to 25% of monthly income may be lost due to poultry disease [2]. Chicken have developed different responses to counter these diseases. These responses include immunological and genetic responses of the poultry. The genetic interaction between the host and the pathogen is a key factor in deciding the disease resistance. The chicken karyotype includes 38 autosomes, many of which are relatively small and uniform in size, often termed microchromosomes. Current knowledge of chicken immunogenomics such as the quantitative trail locus (QTL) mapping of the combination of DNA variations, immune response by the host and the transcriptome can be used to identify disease resistant genes. Disease resistant genes are those encoding antibodies, microRNA and other materials that help the host resist the damage caused by pathogens. Recent advances in the field of molecular biology have led to the discovery of many disease resistant genes. In poultry, genes such MHC (major histocompatibility complex) genes, the Nramp1 (Natural resistance-associated macrophage protein 1) gene, IFN (Interferon) genes, Mx (Myxovirus-resistance) genes, anti-ALV (Avian leucosis virus) genes and the Zyxin gene have been linked to disease resistance [3]. In most of the multicellular organisms single-nucleotide polymorphisms, insertion/deletion polymorphisms, and copy number variations (CNVs) are the major sources of genetic and genomic structural variations [4]. These genetic variations may be exploited to study the diseases resistance levels in different organisms. Recent advances in the technology and cost effectiveness of genotyping, genomic selection approach has been followed extensively for animal breeding. The discovery of chicken genome and development of chicken transcriptome and proteome analysis has led to a better understanding of the mechanisms underlying the genetic susceptibly and resistance against different diseases. Genetic enhancement of the immune response can increase vaccine efficacy and disease resistance, thereby reducing drug residues in food. In order to reduce the drug residues in the food and introduce the genetic breeding programs for improving the disease resistance in the chicken we need to have a better understanding of the disease resistant genes. Also, breeding for disease resistance requires tools such as indicator traits or genetic markers that can be used for selection. Some diseases that have been found to cause serious economic loses to poultry industry in terms of morbidity and mortality are discussed below.
2. Salmonellosis
Among the different diseases occurring in poultry, those caused by the genus
2.1. Genes involved in resistance to Salmonellosis
Many genes have been found to contribute towards resistance against bacterial infections. Some of the main genes involved are Major histocompatibility complex (MHC) genes, Caspase1 genes, NRAMP Family encoding genes, inducible nitric oxide synthase (iNOS) gene, genes encoding complement proteins and Toll-like Receptor 4 (TLR4) genes. Major histocompatibility complex studies have shown that different MHC-B haplotypes contribute differently towards the genetic resistance against salmonellosis. Also microsatellite analysis has shown that MHC-1 class has been linked to
3. Avian influenza virus
Avian/Bird flu, caused by avian influenza virus (AIV) belonging to Orthomyxoviridae family, is the most fearful viral disease of birds and has a potential to cause a detrimental effect on poultry flocks. This disease is of great economic, zoonotic importance and may also lead to pandemic threats. This virus can lead to disease that may range from subclinical symptoms to highly virulent pathogenicity in poultry birds. The frequent disease outbreaks caused by avian influenza virus (AIV) not only affect the poultry industry but also pose a threat to human safety. Based on the level of pathogenicity the disease has been categorised into two groups. The first group is highly pathogenicity avian virus (HPAI) which is highly contagious, and can affect multiple organs. This disease has a potential to spread across national boundaries and is a listed disease of World Organisation for Animal Health (OIE). The second group is low pathogenicity avian virus (LPAI) which is mild disease in poultry that causes mild clinical symptoms like depression and anorexia. Avian influenza virus (AIV) has caused a great economic loss across the globe [25]. The AIV mostly gets amplified in poultry at live poultry markets and finally disseminates to humans [26]. While replication of LPAI occurs in epithelial cells of respiratory and gastrointestinal tract, HPAI replicates in multiple tissues [27]. World Health Organisation has emphasised on the preventive measures to be taken in order to minimise the risk of pandemic influenza and also have highlighted the importance of elucidating the host factors that are related to infection [28]. Currently live or inactivated viral vaccines are used to reduce the incidence of AIV, but these measures are not promising as the efficacy of these vaccines is complicated by different factors which include age/ health status of bird and also the antigenic variant of the virus. So there is an urgent need to develop promising and long lasting strategies to combat these viral diseases. To complement current approaches against AIV, development of poultry flocks that are AIV resistant can be used as a proactive measure to control epidemics and pandemics of influenza in both avian and human populations.
3.1. Genes involved in avian influenza virus
Many studies have been carried out to figure out different disease resistant mechanisms and genes in AIV. Previous studies on Beijing-You chicken have revealed 39 SNPs associated with different immunological traits against avian influenza virus. An important QTL was found on chromosome 16 that was related to total Igγ concentration. Also five candidate genes that were related to Igγ levels were found that might play a role in immune modulation of birds infected with AIV. Different candidate SNPs for marker assisted selection for disease resistance have been identified. The candidate genes play a vital role in regulating immunological response in chicken [29]. Approaches like RNA interference (RNAi) technology can be used to develop transgenic poultry that are resistant to AIV. Synthetic RNA duplexes (siRNA) can be used to trigger RNAi [30]. Also RNAi can be triggered by expression of RNA duplexes in hairpin structures (shRNA) [31] which by RNA endonucleases can be processed into siRNA. While working on cell lines, chicken embryos, synthetic RNA duplexes specific for conserved domains of the influenza virus genes have been found to inhibit replication of various influenza viruses. [32, 33]. Stable expression of influenza-specific shRNA via a lentiviral vector in a cell line renders the cells refractory to influenza virus infection [33]. After introduction of the above mentioned lentiviral vector into mouse lung, an inhibition in virus production was observed
4. Marek’s disease
Marek’s disease (MD) is a neoplastic disease in chickens, caused by the Marek’s disease virus (MDV). Marek’s disease virus (MDV) is an alpha herpes virus that targets avian species and establishes chronic infection. It is a highly contagious lymphotropic disease that remains an important source of economic losses to the world poultry industry since it was first reported by Joseph Marek [35]. Marek’s disease signs include depression, wasting, loose watery stool, paralysis, lymphomas and severe immunosuppression. Although vaccination programs have been used to control onset of the disease, MDV still replicates in vaccinated chicks. These highly contagious cell free virions are continuously shed in the environment. This makes MDV environmentally persistent as well as a highly infectious [36]. Continuously more virulent MDV strains evolve that makes the current vaccination programs ineffective and urge for a need to develop strategies that will augment existing MDV control strategies [37].
4.1. Genes involved in resistance to Marek’s disease
The genetics of the host response to the MDV have been studied for many years. Many loci have been known to be involved in disease resistance but only few genes have been identified to have an actual role. Major histocompatibility complex plays a vital role in resistance against MD [38]. Being a polygenic trait, many genes and gene loci have been reported to be involved in MD resistance. Major histocompatibility complex is one among gene/loci to be involved in genetic resistance against MD. Other genes that are non MHC in origin have also been linked to play a role in genetic resistance/susceptibility to MD. These genes include growth hormone gene, cytokines (IL 6 and IL 18) and the stem lymphocyte antigen 6 complex, LY6E gene. Loci rs14527240 and GGaluGA156129 have been reported to play a role in host resistance/susceptibility to MD. Also expression studies suggest a possible role of SMOC1 gene in MD susceptibility [39]. Nitric oxide which apart from being a promising antiviral agent, also plays a role in modulating immunological responses. While working on Marke’s disease it was found that chickens resistant to MD have the ability to produce more nitric oxide than susceptible chicken lines. The above observation was made by measuring nitric oxide levels from the chicken fibroblasts that were taken from these chicken lines after treatment with LPS and recombinant Chicken IFN-γ. Further plasma nitric oxide levels were measured in chicken lines (N2a, P2a) inoculated with JM-16 strain of MDV. The levels of NO were found to be increased in N2a chickens in majority of the experiments carried out (four out of five). In comparison, in only one experiment the levels of NO were found to be elevated in P2a chickens that too at 10th day post infection. The level of the NO production was found to be associated with the range of virulence of the MDV strain. Inoculation with more virulent strains induced highest NO level which suggests the possible role of NO during the disease progression. Quantitative real time PCR studies show that IFNγ does not primarily induce iNOS gene expression during MDV infection. Nitric acid production and inducible nitric oxide gene expression are mediated during cytolytic phase of infection. These findings suggest that NO may play a role in increasing MDV virulence by suppressing immune system [40]. In order to breed chicken which are genetically resistant to the Marek’s disease, we need to have an ample knowledge about markers that play a role in the resistance to MD. A study was carried to find out the MD resistant markers in chicken lines, copy number variation (CVN) were studied in inbred MD resistant and susceptible chicken lines. In four chicken lines 45 copy number variations were found, out of which 28 CVNs were involved in cellular proliferation and immunological responses. Also two CVNs that were found to be associated with resistance to MD were transmitted to the descendent recombinant congenic lines that differ in MD susceptibility. These observations may be useful for designing better and reliable strategies to improve genetic disease resistance in poultry.
5. Newcastle disease
The causative agent of Newcastle Disease is Newcastle Disease virus (NDV) which belongs to paramyxovirus and is a negative sense RNA consisting of about 15 × 103 nucleotides [41]. This is an enormous destructive and contagious disease that causes serious problems in poultry industry across the globe. Among different poultry diseases NDV was reported to be the fourth most destructive disease that led to heavy loses to poultry industry [42]. Newcastle Disease was considered to be most widespread disease in animals along with rabies and bovine tuberculosis [43]. After infection with NDV the host comes up with non-specific symptoms which include ruffled feathers, depression, breathing problems, anorexia, hyperthermia and listlessness followed by death. Affected chicken show respiratory and neurological complications and also reduction in egg production. Chicken infected with NDV are able to raise an antibody and gene response. The antibody response varies in different chicken breeds, hence understanding the genetics of the immune response may help in improving diseases resistance in chicken [44].
5.1. Genes involved in resistance to Newcastle disease
A study was conducted to elucidate the host antibody response towards NDV. A novel QTL locus that was found to be associated with antibody response was found. From the proximal end of GGA1 this QTL region was located approximately 100 Mb away. This region was proposed to play an important role in immune response of the chicken. Two genes namely ROBO1 and ROBO2 were thought to be promising candidate genes that might have a role in modulating antibody response in chicken infected with NDV. For further confirmation of the role of these genes, studies that include silencing and over expression of ROBO 1& ROBO2 need to be carried out both
6. Conclusion
For effective control of different infectious diseases in chicken, the best and most reliable approach is the improvement of the genetics of disease resistance. Enhancement of immune responses may lead to improved efficacy of vaccines and disease resistance, hence reduction in drug residues in the food products. Introducing new technologies that will help us to unveil the underlying transcriptional and other molecular mechanisms for disease resistance in chicken is a promising tool to improve genetic resistance for diseases. Technologies that aid in identification of disease resistant genes include next generation sequencing, microarray analysis, RNA sequencing and high density SNP genotyping. The development and distribution of disease resistant poultry flocks represents a proactive strategy for controlling diseases in chicken and complements current approaches for disease control by drugs and vaccination.
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