Core Viewpoint - The article discusses the significant role of respiratory viruses, particularly coronaviruses and influenza viruses, in global pandemics and their impact on public health, emphasizing the importance of understanding immune responses and potential antiviral strategies [1][2]. Group 1: Immune Response and Interferon - The innate immune response, including interferons (IFN) and interferon-stimulated genes (ISG), serves as the first line of defense against viral attacks [2]. - Delayed or impaired type I interferon (IFN-I) responses are notable characteristics of severe COVID-19 and influenza infections, with 3.5% of life-threatening COVID-19 patients exhibiting harmful mutations in interferon system genes [2]. - In critical COVID-19 patients, nearly 15% have been found to possess neutralizing antibodies against their own interferons, indicating a significant immune response issue [2]. Group 2: GALNT2 and Antiviral Mechanism - A recent study published in Nature Microbiology identifies GALNT2 as an ISG with broad antiviral activity, establishing it as a crucial defense factor against respiratory virus infections [3][9]. - GALNT2 inhibits the replication of various coronaviruses and influenza viruses, promoting viral clearance and reducing disease severity through O-glycosylation of viral proteins [6][9]. - The mechanism involves GALNT2 modifying the spike protein of SARS-CoV-2, preventing its cleavage by proteases, thus blocking virus-host cell fusion [6][7]. Group 3: Genetic Insights and Implications - Analysis of human genetic data reveals that individuals with GALNT2 gene mutations that impair antiviral function have a significantly higher risk of hospitalization after SARS-CoV-2 infection [8]. - The findings deepen the understanding of host-virus interactions and provide new targets for developing broad-spectrum antiviral strategies against respiratory pathogens [10].

Core Viewpoint - The study reveals that maternal immune activation due to viral infection leads to abnormal secretion of extracellular granzyme B (GzmB) by natural killer (NK) cells, which crosses the maternal-fetal barrier, resulting in the accumulation of fetal macrophages and activation of microglia, ultimately causing neurodevelopmental disorders and behavioral defects in offspring [2][3][6]. Group 1: Research Findings - Maternal NK cells activated by viral infection promote the accumulation of activated macrophages in the fetal brain, leading to neurodevelopmental disorders and behavioral defects in offspring [3][6]. - Extracellular granzyme B (GzmB) is released by maternal CD49a+ tissue-resident NK cell subsets under type I interferon stimulation, crossing the maternal-fetal barrier and promoting the accumulation of fetal macrophages expressing interferon-stimulated genes (ISG) and activation of microglia [3][6]. - Targeting extracellular GzmB by systemic administration of serine protease inhibitor Serpina3n or knocking out the GzmB gene in maternal NK cells can alleviate neuroimmune disorders in the fetal brain induced by maternal immune activation [3][6]. Group 2: Implications - The findings indicate that exposure to a disrupted maternal environment reprograms the immune function of decidual NK cells, disrupting the neuroimmune balance in the fetus and increasing the risk of neurodevelopmental disorders in offspring [6].