2'-5' Oligoadenylate Synthetase-Like 1- (OASL1-) deficient mice promote antiviral protection against Pseudorabies Virus Infection through robust production of type I interferons

Figure 1. Upregulation of OASL1 following PRV infection, observed both in vivo and in vitro. (A) WT mice were injected with either PBS or varying doses of PRV. Survival rates and body weight changes were monitored for up to 7 dpi. (B) WT mice were infected with PRV, and the expression levels of OASL1, IFN-α, and IFN-β were quantified using quantitative real time- polymerase chain reaction (qRT-PCR). (C) Expression levels of OASL1 and type I IFN in primary myeloid cells infected with PRV at varying multiplicities of infection (MOIs) for 24 h.

Figure 2. Enhanced resistance to PRV and reduced viral burden in Oasl1⁻/⁻ mice. (A) Schematic illustration of the experimental setup. (B) The image shows the clinical symptoms. (C) The survival rate, body weight changes, and clinical scores were monitored for up to 12 days. (D) Virus titers in spleens, lungs, and brains of infected mice were determined using qRT-PCR. (E) Type I IFN levels in the serum were measured by ELISA.

Figure 3. Effects of Oasl1⁻/⁻ on pro-inflammatory mediators in PRV infection as determined by qRT-PCR. mRNA expression of pro-inflammatory mediators in spleens, lungs, and brains of infected mice was assessed.

Figure 4. Oasl1⁻/⁻ mice exhibit reduced inflammation following PRV infection. Sandwich ELISA determined protein levels of pro-inflammatory mediators in the spleens, lungs, brains, and serum of PRV-infected mice.

Figure 5. Oasl1⁻/⁻ mice exhibit less severe pathological alterations following PRV infection. Representative hematoxylin and eosin-stained (H&E) tissue sections of PRV-infected Oasl1⁻/⁻ and WT mice are shown. The arrows indicate diminished white pulp and depletion of immune cells in the spleen. Asterisks mark peri bronchial infiltration of inflammatory cells in the lung. Neurodegeneration was significantly observed in the hippocampus neurons of the brain.

Figure 6. Increased Type I IFN Secretion via IRF7 Signaling in PRV-infected Oasl1⁻/⁻ Mice. (A) mRNA expression patterns of IRF7 and IRF3 in spleen, lung, and brain tissues of WT and Oasl1⁻/⁻ mice post-PRV infection evaluated by qRT-PCR at 2, 3, and 4 dpi. (B) Western blot analysis of tissue lysates from the above tissues of WT and Oasl1⁻/⁻ mice illustrating relative protein levels of IRF7 and IRF3.

Figure 7. OASL1-ablated myeloid-derived cells produce elevated levels of type I IFNs after PRV infection. Primary bone marrow-derived macrophages (BMDMs) isolated from WT and Oasl1⁻/⁻mice were infected with PRV at MOIs of 0.1, 0.5, 1, and 5 at the indicated times. (A-B) The mRNA expression of cytokines, chemokines, and IFN-α/β was evaluated via real-time qRT-PCR. (C) The mRNA expression levels of IRF7 and IRF3 in BMDM following PRV infection. (D) The protein expression levels of IRF7 and IRF3 in BMDMs infected with PRV at MOI 0.5 at 24 dpi.