1. Avian Influenza Virus

Daniel R. Perez, Silvia Carnaccini, Stivalis Cardenas-Garcia, Lucas M. Ferreri, Jefferson Santos and Daniela S. Rajao

Influenza is one of the most devasting respiratory diseases of poultry. Avian influenza (AI) is a viral disease caused by influenza A viruses (IAVs) that affects the respiratory, digestive, and nervous systems of several bird species, including domestic poultry and wild aquatic birds. The World Organization for Animal Health (OIE) has included highly pathogenic avian influenza (HPAI) as a List A notifiable disease. The past couple of decades have seen a sharp increase in the number of AI outbreaks, which have led to devastating economic losses in the poultry industry as a direct result of infection, as well as trade limitations and public opinion repercussions. AI also has public health implications, in particular zoonotic strains that have emerged in southeast Asia with the ability to cause lethal infections in humans and, therefore, are of great pandemic concern. Over the past two decades, particularly with the development of reverse genetics systems for influenza viruses, we have learned a great about the mechanisms involved in pathogenesis and transmission of avian-origin influenza viruses in birds and humans. Avian influenza surveillance efforts around the world have provided the discovery of novel hotspots of influenza activity in wild birds as well as novel influenza A viruses in fruit bats and have greatly improved our understanding of the ecology and the evolution of these viruses. Novel and upcoming sequencing technologies are allowing pen-side diagnostics and rapid phylogenetic characterization of influenza viruses from a variety of sources and animal species. Improvements in vaccine technologies and vaccination regimens are paving the way for more efficient control of AI in poultry. Yet, many challenges remain. It is the objective of this chapter to provide an overview of what is known about AI and its implications for animal and human health.

2. Newcastle Disease Virus

Siba K. Samal

Newcastle disease (ND) is a highly contagious avian disease with worldwide distribution that causes severe economic losses in the poultry industry. ND is a notifiable disease throughout the world. The economic impact is not only due to loss of birds, but also due to trade restrictions and embargoes placed on areas and countries where the outbreaks have occurred. In many developing countries, ND is enzootic, and the disease has the greatest impact on villages where the livelihood of people depends on poultry farming. Current vaccines provide protection from clinical signs and mortality but do not prevent virus infection and subsequent virus shedding. Therefore, development of an optimal vaccine is a high priority. ND is caused by virulent strains of Avian avulavirus 1, which are called Newcastle disease virus (NDV). NDV is an enveloped, non-segmented, negative-sense RNA virus belonging to the genus Avulavirus in the family Paramyxoviridae. NDV has been used as a model virus to study the molecular biology of paramyxoviruses. Many of the fundamental properties of paramyxovirus biology are founded on studies of NDV. In recent years, NDV has drawn a lot of research interest not only because it is an important pathogen of poultry, but also because it is an oncolytic agent and a potential vaccine vector for human and animal pathogens. This chapter reviews our current knowledge of NDV as an infectious agent, the immune response to infection and its epizootiology, prevention and control measures.

3. Avian Paramyxoviruses Other Than Newcastle Disease Virus

Anandan Paldurai and Siba K. Samal

Avian paramyxovirus (APMV) serotypes, other than APMV-1, are wide spread in wild bird populations and are occasionally found in poultry. Most of our research has focused on APMV-1 because it includes Newcastle disease virus (NDV), which causes a severe disease in poultry. However, very little research has been done to understand the host range, genetic diversity and pathogenicity of other APMV serotypes. Some of the other APMV serotypes are associated with mild respiratory disease and decreased egg production in poultry. In the last few years, these viruses have gained much attention because of isolation of many novel APMV serotypes. Currently, there are 13 officially recognized APMV serotypes, and another eight putative APMV serotypes. These APMV serotypes are genetically, antigenically and biologically different. Some of these serotypes appear to be present in specific wild bird species, although other wild and domestic bird species are susceptible. Our understanding about this group of viruses has improved significantly in the last decade because of availability of their full genome sequence information. Reverse genetic systems have also been developed for some of these APMV serotypes. The goal of this chapter is to review our current knowledge of this group of avian viruses.

4. Avian Metapneumoviruses

Paul A. Brown and Nicolas Eterradossi

Avian metapneumoviruses (AMPV), discovered in the late 1970s in South Africa, and now detected in almost all parts of the world, are classified in the order Mononegavirales, family Pneumoviridae, genus Metapneumovirus, together with the more recently identified human metapneumovirus (HMPV). AMPVs are responsible for respiratory diseases in poultry resulting in high morbidity and variable mortality depending on the severity of bacterial secondary infections. In breeding birds, a drop in egg production, and quality of egg, can often follow. To date, four subgroups have been defined (A, B, C and D) based on genetic and antigenic properties for which differential laboratory diagnostic tools have been developed. The principal host species of AMPV are turkeys, chickens and ducks, although other bird species can be infected. Subgroup susceptibility changes with bird species. Subgroup C viruses appear to have the broadest host range and, interestingly, show a closer genetic relationship to HMPV than to other AMPV subgroups. This cross-species genetic resemblance between AMPV-C and HMPV reflects common ancestry and a comparative virological approach may improve our understanding of both viruses within the frame of future 'one health' metapneumovirus projects. Conversely, significant differences between AMPV subgroups A, B, D and AMPV-C suggest that knowledge gained from studies of either group of AMPVs may not be readily transferred to the other. A good level of protection against AMPV infection can be achieved in chickens or turkeys by careful vaccination using a combination of live attenuated and inactivated vaccines, together with good farm practices; however, several studies have shown that some live vaccines can revert to virulence causing problems in the flock. To address this, attempts have been made to generate more stable live vaccines with reverse genetics, yet still no recombinant AMPV vaccine has been commercialised since the development of the first system in 2004. This chapter gives an up-to-date review of the literature and perspectives for AMPV.

5. Infectious Bronchitis Virus

Ding Xiang Liu, Yan Ling Ng and To Sing Fung

Infectious bronchitis virus (IBV) is one of the major avian viral pathogens that afflict the global poultry industry. Since its first isolation in 1931, astounding numbers of IBV variants have been identified around the world. With the continuous emergence of pathogenic variants and the lack of efficacious IBV vaccines that provide a broad spectrum of protection, it is crucial to study and understand the biology of this economically important pathogen. In fact, using IBV as a prototype coronavirus, research over the past few decades have unravelled some of the most fundamental concepts in the molecular cell biology and pathogenesis of coronavirus. Also, IBV is among the few coronaviruses that reverse genetics systems were first successfully established. In this chapter, we first briefly revisit the history of IBV, followed by an up-to-date review of its molecular biology and effects on the infected cells, with a focus on the molecular mechanisms of viral replication and the strategies exploited by this virus to regulate and interact with critical cellular signalling pathways, such as ER stress response, autophagy and apoptosis. We then review the pathogenesis of IBV, and end with a discussion on the current status of IBV epizootiology, prevention and control.

6. Avian Reovirus

Frederick S.B. Kibenge, Yingwei Wang, Molly J.T. Kibenge, Anil Kalupahana and Scott McBurney

Avian reoviruses, including all orthoreoviruses of avian origin, belong to the genus Orthoreovirus, one of 15 recognized genera in the family Reoviridae, with a double-stranded RNA genome of 10 segments and a non-enveloped double-layered icosahedral capsid. Avian reoviruses are very common among commercial poultry and other avian species and are also important avian pathogens causing a variety of pathological conditions the most common being viral arthritis/tenosynovitis in commercial broiler chickens and turkeys, and enteric disease and neurological disease in wild birds. These viruses have been extensively studied, as evidenced by the extensive list of published literature reviewed in this chapter. The application of the recently reported reverse genetics system using avian reoviruses will significantly increase our understanding of avian reovirus biology and disease.

7. Infectious Bursal Disease Virus

Shijun J. Zheng

Infectious bursal disease (IBD), also called Gumboro disease, is an acute, highly contagious and immunosuppressive poultry disease caused by IBD virus (IBDV). The immunosuppression as a consequence of IBD increases susceptibility to other microbial infections and the risk of failure in subsequent vaccinations against other diseases. This disease still threatens the poultry industry worldwide, and in particular the frequent emergence of very virulence or variant IBDV strains in vaccinated flocks causes severe economic losses to stakeholders. The genome of IBDV is relatively small, encoding a limited number of proteins that inhibit host antiviral response and induce apoptosis in proliferating B lymphocyte in the bursa of Fabricius (BF), directly breaking down the immune system of infected birds. The virulence factors are crucial for IBDV to avoid host defences and survive as a successful pathogen. Insights into the roles of these viral proteins and cellular microRNAs (miRNAs) in host response will add to the understanding of the pathogenesis of IBDV infection and provide clues to a rational design for safer and effective novel vaccines. This chapter focuses mainly on our current knowledge of IBDV as an aetiological agent of IBD, the virus-host interactions at the protein and the miRNA levels during IBDV infection, and control of IBD by vaccination.

8. Avian Leukosis Virus

Yongxiu Yao and Venugopal Nair

The leukosis/sarcoma (L/S) group of diseases comprise of a variety of transmissible benign and malignant neoplasms, such as lymphoid, myeloid and erythroid leukosis, caused by avian leukosis viruses (ALV), belonging to the family Retroviridae. Extensive research in the last several decades have uncovered interesting biology of these viruses and their pathogenic mechanisms. ALV are characterized by the unique possession of a reverse transcriptase enzyme that drives the generation of the DNA provirus, which is integrated into the host genome during viral replication, and induction of diseases is from insertional activation as well as transduction of oncogenes such as c-myc. ALV-associated diseases are widespread with significant economic losses resulting from tumors and subclinical infections and loss of productivity. ALVs infecting chickens belong to six envelope subgroups A, B, C, D, E (endogenous retroviruses) and J, with A, B and J subgroups the most important ones in terms of distribution and induction of diseases. While A and B subgroups are primarily associated with lymphoid leukosis, ALV-J primarily induces myeloid leukosis, currently a major problem in countries such as China. With the virus transmitted both vertically through the eggs from infected hens and horizontally, prevention of the disease is mainly by preventing the introduction of viruses and by eradication, taking advantage of the diagnostic tests to identify and disrupt the infection cycle. Genetic resistance to ALV infection has also been observed primarily based on the presence or absence of specific receptor sequences. Recent advances in genome editing offers the possibility of exploiting genetic resistance in the fight against ALV.

9. Chicken Infectious Anaemia Virus

Karel A. Schat

Chicken anaemia virus (CAV) is the only member of the genus Gyrovirus of the family Anelloviridae. It has a single-stranded, covalently linked circular DNA genome of 2.3 kb coding for three viral proteins (VP). VP1 forms the capsid and is the only protein in the virus particles. VP2 has multiple functions, which are essential for the formation of the virus particles. VP3 causes apoptosis in vitro and in vivo. VP3, also known as Apoptin, is investigated as a potential anticancer treatment for human tumors. The promoter/enhancer region resembles oestrogen response elements and transcription can be activated by oestrogen and repressed by chicken ovalbumin upstream promoter transcription factor 1. Viral DNA can remain present in the gonads of chickens with or without virus-neutralizing (VN) antibodies. Transfer of viral DNA through the embryo can occur independently of the presence of VN antibodies. Infection of 1-day-old chicks without maternal antibodies causes apoptosis of the haematopoietic cells in the bone marrow and thymocytes in the thymus cortex causing anemia and immunosuppression. Infection after 2 to 3 weeks of age does not cause clinical disease but may cause subclinical immunosuppression. Vaccination of pullets between 9 and 15 weeks of age prevents clinical disease in newly hatched chickens by the transfer of maternal antibodies.

10. Avian Adenoviruses

Eva Nagy

Avian adenoviruses are ubiquitous worldwide in avian species. Although many of these viruses are isolated from healthy birds, some cause diseases associated with significant economic losses in the poultry industry, including egg-drop syndrome (EDS), inclusion body hepatitis (IBH), inclusion body hepatitis/hydropericardium syndrome (IBH/HPS) in chickens and hemorrhagic enteritis (HE) of turkeys. Avian adenoviruses are classified into three genera based on genome organisation, phylogenetic relationships and host: Aviadenovirus, Atadenovirus and Siadenovirus. The viral genome consists of genus-common and genus-specific genes. Genus-common genes, such as those involved in DNA replication and encoding structural proteins, are conserved and present in all adenoviruses. Genus-specific genes, on the other hand, are unique for each genus. The functions of most early viral genes of avian adenoviruses remain unknown. Some of these genes, such as Gam-1 and ORF22, have functions similar to those described for human adenoviruses - stimulation of cell cycle progression, modulation of apoptosis and counteraction of the host's innate immunity. Studies on virus-host interactions at the molecular level are limited to a few viruses [e.g. fowl adenovirus (FAdV)-1, FAdV-4 and FAdV-9]. The virulence determinants for these viruses are unknown. However, some candidate viral genes associated with virulence have been described in some aviadenoviruses (e.g. FAdV-4 and FAdV-8) and a siadenovirus (duck adenovirus 1). Non-pathogenic aviadenoviruses, such as fowl adenoviruses 1, 4, 8, 9 and 10, have been described as virus vectors for potential use as recombinant poultry vaccines and gene delivery.

11. Infectious Laryngotracheitis Virus

Mauricio J. C. Coppo, Amir H. Noormohammadi and Joanne M. Devlin

Infectious laryngotracheitis (ILTV) is an alphaherpesvirus that causes economically significant respiratory disease in poultry industries worldwide. The disease was reported as early as the mid-1920s. A strong research focus on control measures, including the development of vaccines and diagnostic tests, has helped to limit the impact of this disease; however, ILTV infection nevertheless remains prevalent in many poultry producing areas. Recent advancements in whole genome sequencing and bioinformatic analyses of genome sequences have contributed much to our understanding of ILTV, including the epizootiology of the disease. Furthermore, recent advances in vaccine development, including the availability of vectored vaccines, have provided additional tools to help control ILTV in the field. A number of key gaps in our understanding of ILTV still remain and these can limit our ability to effectively control this disease.

12. Marek's Disease Virus

Blanca M. Lupiani, Yifei Liao, Di Jin, Yoshihiro Izumiya and Sanjay M. Reddy

Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens, causing enormous economic losses to the poultry industry. MDV belongs to the genus Mardivirus and is classified into three serotypes. Only viruses belonging to serotype 1 cause disease in chickens. In susceptible chickens, T-lymphocytes undergo neoplastic transformation. The manifestation of the disease depends on the distribution of the neoplastic lesions. Typically, the disease is manifested by visible lymphomas in various visceral organs and paralysis. Highly pathogenic MDV also causes neurological disease and immunosuppression. MDV is controlled by vaccination using live attenuated vaccines, but vaccinated chickens do not provide sterilizing immunity and cannot block virus transmission of field strains. Vaccination is generally believed to have contributed to increase in virulence of the filed strains leading to vaccine breaks. Among several genes encoded by MDV, meq, which encodes a bZIP protein, appears to play a critical role in the transformation of lymphocytes. With the availability of genome manipulation tools and a natural host system, MDV provides a relevant model to explore the molecular mechanisms of viral oncogenesis. In this chapter, we summarize the current knowledge of MDV molecular biology, pathogenesis and control, as well as the role of individual viral genes in replication and transformation.

13. Avian Pox Viruses

Deoki N. Tripathy

Avian pox viruses infect both wild and domestic birds. In this regard, more information is available on fowlpox virus type species of the genus Avipoxvirus because of its economic impact on commercial poultry. Canarypox virus infection causes high mortality in canaries. The diagnosis is based on the development of cutaneous and/or diphtheritic lesions and histopathologic examination of the lesions for cytoplasmic inclusions. The virus multiplies in the cytoplasm of infected cells and produces cytoplasmic inclusion bodies. Virus isolation is carried out in the developing chicken embryos. Complete nucleotide sequence of the genomes of fowlpox virus, canarypox virus and few other avian pox viruses has been determined. Polymerase chain reaction (PCR) is being used to amplify nucleotide sequences of specific genes, e.g. 4b, for diagnosis and phylogenetic analysis of strains. For disease prevention, vaccines of fowlpox and pigeonpox virus origin have been used for many years by the poultry industry. Outbreaks of fowlpox in previously vaccinated chickens still occur in many poultry operations. The virus strains isolated from such outbreaks show insertion of full-length reticuloendotheliosis virus (REV) in their genome. REV has been associated with immunosuppression and tumor formation. It appears that the emerging strains are antigenically and genetically different for which the current vaccines do not provide adequate protection.

14. Avian Immune Responses to Virus Infection

Lonneke Vervelde and Jim Kaufman

All organisms have evolved a large number of complicated and interwoven immune responses to defend themselves against a wide variety of pathogens. The vast majority of what is known about immunity is from research on humans and biomedical model species. However, the challenges faced by the poultry industry because of infectious diseases from viruses has driven research over many decades. Innate immunity consists of many different systems dependent on a wide variety of host genes, provides the initial stages of response against all pathogens, can provide protection in individuals with the appropriate host alleles, and is crucial for initiation and guidance of the adaptive immune system. Adaptive immunity is particularly important as the basis for vaccination, in which innate immunity is stimulated by adjuvants present in the vaccines. However, the genetics of adaptive immunity can also be important, as resistance to many economically important viruses is dependent on particular generalist alleles of the molecules encoded by the major histocompatibility complex (MHC). Further research should elucidate the molecular bases for both innate and adaptive immune responses, allowing better genetic breeding, improved vaccines and application to birds outside of the poultry industry.