African Swine Fever Virus pF778R Attenuates Type I Interferon Response by Impeding STAT1 Nuclear Translocation

In this study, we discovered a negative regulation of the type I interferon (IFN) response by the ASFV ribonuclease reductase large subunit pF778R. This novel type Ⅰ IFN response antagonist significantly inhibits IFN-α-induced interferon-stimulated response element promoter activation, precludes the upregulation of various interferon-stimulated genes, and prevents STAT1 nuclear translocation. Mechanistically, pF778R did not affect the protein levels of crucial molecules in the JAK/STAT signaling pathway or engage in direct interactions. However, pF778R expression impedes type I IFN responses mediated by the JAK/STAT signaling pathway. Further investigations revealed that pF778R did not interfere with STAT1 phosphorylation or dimerization, but it inhibited IFN signaling by weakening the nuclear accumulation of activated STAT1. The critical role of the ASFV protein pF778R in evading IFN-I-mediated innate immunity highlights a unique mode of ASFV evasion and provides insights into the pathogenic mechanism of the virus.PMID:37536381 | DOI:10.1016/j.virusres.2023.199190

Source: Virus Research - August 3, 2023 Category: Virology Authors: Qichao Chen Liang Li Lixinjie Liu Zhankui Liu Shibang Guo Chen Tan Huanchun Chen Xiangru Wang Source Type: research