The Interferon-Inducible Mouse Apolipoprotein L9 and Prohibitins Cooperate to Restrict Theiler’s Virus Replication

Abstract

Apolipoprotein L9b (Apol9b) is an interferon-stimulated gene (ISG) that has antiviral activity and is weakly expressed in primary mouse neurons as compared to other cell types. Here, we show that both Apol9 isoforms (Apol9b and Apol9a) inhibit replication of Theiler’s murine encephalomyelitis virus (TMEV) but not replication of vesicular stomatitis virus (VSV), Murid herpesvirus-4 (MuHV-4), or infection by a lentiviral vector. Apol9 genes are strongly expressed in mouse liver and, to a lesser extent, in pancreas, adipose tissue and intestine. Their expression is increased by type I interferon and viral infection. In contrast to genuine apolipoproteins that are involved in lipid transport, ApoL9 has an intracytoplasmic localization and does not seem to be secreted. The cytoplasmic localization of ApoL9 is in line with the observation that ApoL9 inhibits the replication step of TMEV infection. In contrast to human ApoL6, ApoL9 did not sensitize cells to apoptosis, in spite of the presence of a conserved putative BH3 domain, required for antiviral activity. ApoL9a and b isoforms interact with cellular prohibitin 1 (Phb1) and prohibitin 2 (Phb2) and this interaction might contribute to ApoL9 antiviral activity. Knocking down Phb2 slightly increased TMEV replication, irrespective of ApoL9 overexpression. The antiviral activity of prohibitins against TMEV contrasts with the pro-viral activity of prohibitins observed for VSV and reported previously for Dengue 2 (DENV-2), Chikungunya (CHIKV) and influenza H5N1 viruses. ApoL9 is thus an example of ISG displaying a narrow antiviral range, which likely acts in complex with prohibitins to restrict TMEV replication.

Tissue and host species-specific transcriptional changes in models of experimental visceral leishmaniasis

“…These genes, of which 25/26 (96%) are interferon responsive, clustered in STRING analysis around 2 nodes ( Cxcl9 and Gbp1 : Figure 12B and C ) and reflected a significant enrichment for GO TERMS including “cellular response to interferon-beta” (GO:0035458, FDR 7.19×10 -8 ), “defence response to protozoans” (GO:0042832, FDR 7.22×10 -8 ), “immune response” (GO:0006955, FDR 9.71×10 -8 ), and symbiont containing vacuole” (GO:0020003, FDR 2.15×10 -9 ). The gene set also contained 3 apolipoprotein L genes ( Apol10a , Apol10b and Apol11b ) which are phylogenetically related amongst the 12 members of the murine Apolipoprotein L family 54 . Of note, 19/26 (73%) genes in this signature were also upregulated in hamster spleen ( Figure 12B ), whereas 6/26 (23%) were upregulated in human whole blood 39 .…”

PKC epsilon‐dependent calcium oscillations associated with metabotropic glutamate receptor 5 prevent agonist‐mediated receptor desensitization in astrocytes

“…They were cloned in pMK117 (Kreit et al . ) using BshTI and EcoRI. This construct also harbours the gene encoding for the fluorescent protein E2‐Crismon, facilitating the detection of infected cells.…”

Analysis of differentially expressed proteins in Muscovy duck embryo fibroblasts infected with virulent and attenuated Muscovy duck reovirus by two-dimensional polyacrylamide gel electrophoresis

“…The protein is reported to be selectively up-regulated in infective pathogen forms which could be critical for disease pathogenesis [ 15 , 23 ]. For example, PHB plays a role in the internalization of Chikungunya virus (CHIKV) as a receptor protein [ 30 ], and was shown to have antiviral activity against Theiler’s murine encephalomyelitis virus (TMEV) [ 12 ]. In the present study, PHB was enriched in all three groups.…”