Question

The authors identify a number of IFNg-stimulated genes in their study. They identify 3 genes they suggest are novel because no one has previously shown that these genes have a role in viral control of (-)RNA viruses. Choose one of these genes, identify its function, and speculate as to how it may control viral replication.

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005263

Answer 1

IFNγ basically blocks the EBOV infection of primary macrophages in wild type mouse

1. M-CSF(macrophage colony stimulating factor)-treated macrophages were primarily investigated in these studies to early target for virus replication.

2. M-CSF-treated peritoneal macrophages cultures that were also pretreated with a combination of IFNγ and TNFα were highly resistant to EBOV infection.

3. The addition of cytokines TNFα and IFNγ to macrophages has been shown to generate a proinflammatory M1 phenotype.

4. Evidence that the combination of these cytokines or IFNγ alone elicited an M1 phenotype of our isolated macrophages included significant increases in expression of proinflammatory genes such as IL-6, TNFα, and CXCL10 in our cells in the presence or absence of EBOV infection.

5. Less well-characterized ISGs that were highly upregulated in our gene array studies were also assessed for their ability to directly control virus infection. Ectopic expression of VAMP5 resulted in significant inhibition of EBOV GP/rVSV.
6. Evaluation of these ISGs for their ability to inhibit EBOV demonstrated that they also effectively blocked EBOV, identifying these as novel ISGs that are likely important for the control of EBOV in IFNγ-treated cells.