Report on Adenovirus Type 4 (FAdV-4) and its Biological Features
Dr. Majed Hamed Al Sayeg / poultry pathologist/ Australia
Introduction
Adenovirus type 4 (FAdV-4) is a highly virulent virus that causes significant economic losses in the poultry industry worldwide. It primarily affects poultry aged 3 to 5 weeks, leading to the syndrome of Hepatitis-Hydropericardium Syndrome (HHS), which is characterized by liver damage and fluid accumulation in the pericardial sac. The virus has spread globally since its first discovery in Pakistan in 1987, undergoing genetic changes, including deletions in its genome, resulting in the emergence of more virulent strains.This report addresses the biological features of FAdV-4, including its genome structure, the pathogenic mechanism, epidemiology, and the role of key proteins in the virus’s ability to infect. It also discusses the immune response to the virus and current control strategies to manage its spread.
Genome Structure and Structural Features
FAdV-4 belongs to the Adenoviridae family, and it is an uncoated virus with a double-stranded DNA genome approximately 45 kilobases in length. The genome encodes several structural proteins, including hexon, penton base, fiber proteins, and subproteins such as protein IIIa, protein VI, and protein VIII. These structural proteins are crucial for virus formation, attachment to host cells, and immune evasion. Genetic disruptions in structural proteins, particularly hexon and fiber proteins, have been linked to increased virulence of FAdV-4 strains. The FAdV-4 genome also contains non-structural proteins responsible for genome replication and virus assembly. Among these proteins, protein 100K plays an important role in hexon trimers, thereby facilitating the formation of new virions.
Pathogenic Mechanism and Clinical Symptoms
The primary disease caused by FAdV-4 is Hepatitis-Hydropericardium Syndrome (HPS), characterized by yellow fluid accumulation in the pericardial sac, liver necrosis, and in some cases, hemorrhaging in other organs such as the kidneys and spleen. Infected poultry show symptoms of lethargy, drooping feathers, and reduced food intake. The virus primarily targets liver cells, leading to cell death and hepatitis.FAdV-4 infection can result in high mortality rates in broiler chickens, with death rates ranging from 80% to 100%, especially in highly virulent strains. The virus is mainly transmitted orally via fecal-oral routes, and vertical transmission can occur through infected eggs.
Epidemiology
FAdV-4 has spread across continents, with reports of outbreaks in countries such as Pakistan, India, China, Brazil, and the United States. The virus tends to thrive in warm and humid conditions, although outbreaks can occur under different environmental conditions. In recent years, since 2015, outbreaks of highly virulent strains in China have been linked to genetically updated strains, leading to significant economic losses in poultry farms.Genetic analyses of FAdV-4 strains have shown notable differences between Chinese and non-Chinese strains, with a large genetic deletion in Chinese strains, which is associated with increased virulence and rapid disease spread.
Immune Evasion and Immune Response
FAdV-4 has developed mechanisms to evade the host’s immune response, including the suppression of antiviral cytokine expression. The virus interferes with the host’s innate immune system by inhibiting the activity of key proteins such as Protein Kinase R (PKR), which is responsible for antiviral defense. Infected cells show a significant reduction in immune cells, such as T and B cells, leading to immune suppression.The virus triggers an immune response in the host, including the production of inflammatory cytokines such as IL-1β, IL-2, and IFN-γ. These cytokines play a role in host defense against infection, but excessive inflammatory responses can lead to tissue damage and contribute to the pathogenic mechanism.
Co-infection with Other Pathogens
FAdV-4 is often associated with co-infection with other pathogens, such as Infectious Bursal Disease Virus (IBDV), Chicken Infectious Anemia Virus (CIAV), and Avibacterium paragallinarum. Co-infections exacerbate the disease, leading to higher mortality and more severe clinical symptoms. For example, co-infection with IBDV increases immune suppression, making poultry more susceptible to FAdV-4.In some cases, FAdV-4 also coexists with other avian viruses, such as the Marek’s Disease Virus, leading to more severe symptoms, including fluid accumulation in the pericardium and hepatitis.
Vaccine Development and Control Strategies
Controlling FAdV-4 remains challenging due to its rapid mutation rate and its ability to evade the immune response. Inactivated vaccines have been developed, but their effectiveness is often limited due to the presence of highly virulent strains.Recent studies focus on developing vaccines targeting specific viral proteins, particularly fiber proteins, which are essential for the virus’s attachment to host cells. Recombinant fiber proteins have shown promise in inducing protective immunity in vaccinated poultry, but further research is needed to improve vaccine efficacy.
Conclusion
Adenovirus type 4 (FAdV-4) is a major threat to poultry health worldwide, causing severe diseases and significant economic losses in the industry. The virus’s ability to mutate and escape the immune response, along with its co-infection with other pathogens, complicates control efforts. Continued monitoring and research into its pathogenic mechanism and the development of more effective vaccines are crucial for controlling FAdV-4 outbreaks and protecting the poultry industry.
Future studies focusing on the role of non-coding RNAs (ncRNAs) and their regulatory effects on viral replication could provide new insights into virus control strategies. Additionally, enhancing immune responses by modifying cytokine stimulation may improve the effectiveness of current control measures.
