The Kinetics of gene expression related to innate and adaptive immunity following Newcastle disease virus infection

Newcastle is a highly contagious and acute disease in avian species and causes severe economic losses in its virulent form, it is caused by avian paramyxovirus1, single stranded RNA virus encoding eight gene products which are: nucleoprotein (NP), Phosphoprotein (P), Matrix (M), Fusion (F), Hemagglutinin-neuraminidase (HN), The RNA polymerase (L), V and W proteins.

The HN is crucial for viral entry and release from host cell while F protein facilitate the viral virulence, Both HN and F play crucial role in determining cell fusion, Tropism & virulence characteristics of NDV.

NDV begins to replicate as soon as 2 hours post infection leading to primary viremia as early as 12 hours post infection leading to viral dissemination to other organs. To control NDV both biosecurity and vaccination should be implemented.

Humoral immune response targets the HN & F glycoprotein of NDV, Innate immunity plays a crucial role for the initial response against NDV & to activate viral specific immune response.

Following Viral entry, the host cell uses a range of receptors Known as (PRRs) Pattern recognition receptors in order to interact with the RNA of the virus.

PRRs include:

• Toll-like receptors: TLR3, TLR5 &TLR7
• RIG-I-like receptors: RIG1, MDA5&LGP2
• cGAS
• DDX family (DDX1) & (DDX3X)

The activation of this proteins (Receptors) triggers specific signalling pathways resulting in the induction of interferons and various downstream antiviral proteins & proinflammatory cytokines.

This cytokine plays a very important role in supressing viral replication, The recognition of NDV nucleic acid by chicken toll like receptors initiate signalling cascade which leads to the induction of chicken type 1 interferon which:

• Activate transcription of several chicken interferon stimulated genes (ISG) as Mx1 critical for the antiviral responses
• Synthesis of T helper pro inflammatory cytokine IL6 which facilitate generation and development of B cells (Adaptive immune response)

The role of cytotoxic CD8+ T cells:

• Identify viral peptides presented on MHC1 molecules located on the surface of infected cell.
• This identification leads to the release of cytotoxic substance & antiviral cytokines leading to viral destruction.

Monitoring the transcriptional responses of the host including chINF- α, Mx1, TLR7, TLR5, IL6, MHC-1 and INF-γ Evaluates the capacity of NDV vaccinations to modulate the kinetics of several antiviral and pro-inflammatory cytokines in the presence of vNDV challenges.