TY - JOUR
T1 - Persistent LCMV infection is controlled by blockade of type I interferon signaling
AU - Teijaro, John R.
AU - Ng, Cherie
AU - Lee, Andrew M.
AU - Sullivan, Brian M.
AU - Sheehan, Kathleen C.F.
AU - Welch, Megan
AU - Schreiber, Robert D.
AU - De La Torre, Juan Carlos
AU - Oldstone, Michael B.A.
PY - 2013/4/12
Y1 - 2013/4/12
N2 - During persistent viral infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. We demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic choriomeningitis virus. IFN-I blockade before and after establishment of persistent virus infection resulted in enhanced virus clearance and was CD4 T cell-dependent. Hence, we demonstrate a direct causal link between IFN-I signaling, immune activation, negative immune regulator expression, lymphoid tissue disorganization, and virus persistence. Our results suggest that therapies targeting IFN-I may help control persistent virus infections.
AB - During persistent viral infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. We demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic choriomeningitis virus. IFN-I blockade before and after establishment of persistent virus infection resulted in enhanced virus clearance and was CD4 T cell-dependent. Hence, we demonstrate a direct causal link between IFN-I signaling, immune activation, negative immune regulator expression, lymphoid tissue disorganization, and virus persistence. Our results suggest that therapies targeting IFN-I may help control persistent virus infections.
UR - http://www.scopus.com/inward/record.url?scp=84876311772&partnerID=8YFLogxK
U2 - 10.1126/science.1235214
DO - 10.1126/science.1235214
M3 - Article
C2 - 23580529
AN - SCOPUS:84876311772
SN - 0036-8075
VL - 340
SP - 207
EP - 211
JO - Science
JF - Science
IS - 6129
ER -