Type I IFN signaling blockade during ART-treated and untreated chronic SIV infection suppresses inflammation but does not increase virus replication

Objective: Determine how admnistration of type I IFN antagonist influences the expression levels of interferon stimulated genes (ISG) during ART-treated or untreated chronic SIV infection. Methods: SIVmac251 infectected animals on or off ART received 3.5mg/kg pasylated-IFN-Iant two or three times a week from week 16 to 24 post-infection. RNA was rextracted from PBMC collected at several timepoints around IFN-Iant trearment and analyzed by RNA sequencing to compare transcription between IFN-Iant or placebo animals. Results: ISG, which are involved in control of virus replication, were increased upon SIV challenge and reduced by ART. Administration of IFN-Iant to ART-treated animals resulted in further reduction of ISG expression. Blocking IFN-I signaling in ART-untreated animals resulted in the most prominent reduction of ISG expression. Conclusion: These findings indicate that administration of an antagonist during ART-treated and untreated chronic SIV infection significantly impact IFN-I signalling. 35 animals were infected with SIVmac251. At 8 weeks post infection (p.i.), 25 animals received ART. From week 16-24p.i., 6 ART-untreated animals received 3x weekly IFN-Iant as compared to 4 placebo. In the ART-treated arm, 11 animals received 2xweekly FN-Iant and 5 animals 3x weekly FN-Iant as compared to 9 placebo.