New research on how Marek’s may affect immune system

Researchers from Freie Universität Berlin in Germany explained that MDV infection starts with the inhalation of infectious dust. Mononuclear phagocytes transfer the virus to lymphoid organs, such as the spleen, thymus, and bursa, where the virus lytically replicates in lymphocytes. MDV can establish latency in infected T cells. Latently and/or lytically infected T cells transport the virus to the skin and feather follicle epithelia (FFE), where cell free MDV is generated. In addition, MDV can transform latently infected T cells, resulting in deadly lymphomas.

Marek’s disease virus (MDV) in chickens is estimated to cost the global poultry industry up to USD 2 billion each year. In Asia, economic losses are spiking despite the wide use of vaccines.

In the early stages of disease, MDV directly affects the chicken’s immune system and prevents it functioning correctly, allowing the virus to replicate. Clinically, this impact is known as ‘immunosuppression’, but the exact way MDV does this is unknown.

Recent research carried out at UK’s The Pirbright Institute has led to a greater understanding of MDV and its impact on the poultry immune system, potentially informing new strategies in prevention and control to improve the health and welfare of poultry.

Viruses that evolve to escape the immune system have advantages over the host because they can remain undetected in the body where they can replicate and cause clinical disease. Understanding exactly how they do this is an important part of disease prevention.

COX-2/PGE2 pathway

MDV targets cells known as CD4+ T cells or T helper cells. These cells are a crucial part of the adaptive immune response which helps fight infection and is vital in the creation of cells that will remember the virus if it infects the host again (that way it can fight the infection quicker next time). T helper cells, as their name suggests, help to activate the immune system by releasing chemicals that attract more cells to assemble an army to kill the virus.

“MDV changes CD4+ cells resulting in immunosuppression, but currently we do not know how,” said researchers at Pirbright. They have made another step forward in understanding this in a recent paper published in Frontiers in Immunology.

“There are many cells and pathways involved in immune responses but the focus in this research was the COX-2/PGE2 pathway. This pathway creates prostaglandin E2 (PGE2), which is known to inhibit the activity of T cells during an immune response.

COX-2 is involved in the creation of prostaglandin E2. It was therefore hypothesized that inhibiting the COX-2/PGE2 pathway could reduce the production of prostaglandin E2 and reverse the immunosuppression caused by MDV,” the researchers explained.

Results from this study demonstrate that MDV activates the COX-2/PGE2 pathway in laboratory studies to investigate host-virus interactions in chickens. Findings also suggest that activation of this pathway results in reduced T cell numbers 21 days after virus infection.

However, scientists were able to reverse this effect with a drug called meloxicam, which inhibits COX-2. With COX-2 inhibited, the production of prostaglandin E2 was reduced which prevented suppression of the immune response. This research revealed that the COX-2/PGE2 pathway is important in Marek’s disease and highlights COX-2 inhibitor drugs as potential treatments.

The research also demonstrated that disease causing strains of MDV activated the COX-2/PGE2 pathway but that the vaccine strain of the virus, known as Rispens-CVI988 did not.

“Understanding the role of MDV-induced COX-2/PGE2 activation in the modulation of immune responses against viral infection may lead to the development of novel vaccine strategies. It may also be possible that MDV infection could be used as a model for the development of new treatment strategies, by targeting the COX-2/PGE2 pathway, to control viral replication and virus-induced immunosuppression,” said Dr Shahriar Behboudi, Head of the Avian Immunology Group at Pirbright.

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