Persistent viral infection such as those from HIV, Hepatitis B and Hepatitis C can lead to continuous pain and suffering in infected individuals. Persistent viruses are able to avoid clearance by down-regulating the immune system and suppressing the activation of antiviral CD4 and CD8 T cells. After persistent infection, a hyperimmune response is often observed characterized by elevated pro-inflammatory mediators and a constant interferon signature. Type 1 interferon (IFN-1) signaling is upstream of many immune responses such as activation of T cells, B cells and natural killer cells as well as inflammatory genes. Interferon is a protein that cells display during the presence of pathogens to communicate to other cells and initiate the innate immune system. Interferon signaling is necessary for host defense against viral infection and viral immunity during acute infections.(1) Because of this it is suspected that IFN-1 is responsible for the hyperimmune activity in persistent viral infection.
To understand the role of IFN-1 in persistent viral infection the authors used the Armstrong (Arm) and clone 13 (Cl13) strains of lymphocytic choriomeningitis virus. The Arm strain is characterized by an acute infection, while the Cl13 strain is characterized by a systemic viral infection. Through the use of IFN-β-yellow fluorescent protein tagging in plasmacytoid dendritic cells (pDCs) it was determined that IFN-β was produced during Cl13 infection and not during Arm infection. Fluorescent protein tagging works by attaching an antibody to a cell surface protein receptor. Then an additional molecule that contains the fluorescent tag binds to the antibody attached to the protein of interest thereby allowing you to observe the expression of the target protein, in this case IFN-β .By replacing the glycoproteins of Arm and Cl13 viruses with green fluorescent protein, the authors confirmed that Cl13 infection preferentially targets pDCs. Green fluorescent protein is a protein that is found in jellyfish. We can insert the gene for the green fluorescent protein into the coding sequence of our target protein, then when the protein of interest gets transcribed the green fluorescent protein will be transcribed as well and we can measure target protein levels by measuring the level of green fluorescent protein. pDCs showed increased green fluorescent protein expression when infected with the Cl13 viruses marked with the protein compared to when infected with the Arm viruses marked with the green fluorescent protein.
