Pin-Pointing the Key Hubs in the IFN-γ Pathway Responding to SARS-CoV-2 Infection

Abstract

Interferon gamma (IFN-γ) may be potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-γ pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2-positive and -negative patients, we identified IFN-γ-associated pathways to be enriched in positive patients. Bioinformatics analyses showed upregulation of MAP2K6, CBL, RUNX3, STAT1, and JAK2 in COVID-19-positive vs. -negative patients. A positive correlation was observed between STAT1/JAK2, which varied alongside the patient’s viral load. Expression of MX1, MX2, ISG15, and OAS1 (four well-known IFN-stimulated genes (ISGs)) displayed upregulation in COVID-19-positive vs. -negative patients. Integrative analyses showcased higher levels of ISGs, which were associated with increased viral load and STAT1/JAK2 expression. Confirmation of ISGs up-regulation was performed in vitro using the A549 lung cell line treated with Poly (I:C), a synthetic analog of viral double-stranded RNA; and in different pulmonary human cell lines and ferret tracheal biopsies infected with SARS-CoV-2. A pre-clinical murine model of Coronavirus infection confirmed findings displaying increased ISGs in the liver and lungs from infected mice. Altogether, these results demonstrate the role of IFN-γ and ISGs in response to SARS-CoV-2 infection, highlighting alternative druggable targets that can boost the host response.

Humoral and cellular immune responses after 6 months of a heterologous SARS-CoV-2 booster with the protein-based PHH-1V vaccine in a phase IIb trial

“…IFN-γ is a crucial marker of an induced anti-viral T-cell immune response [13] and plays a central role in fighting SARS-CoV-2 infection [14]. Previously, we have shown that the PHH-1V booster confers an IFN-γ response comparable to BNT162b2 up to day 98 (3 months) [12].…”

Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma

“…The top proteomic contributors in our discriminatory model included interferon-induced GTP-binding protein Mx1 (MX1 or MXA), interferon-stimulated gene 15 (ISG15), Z-DNA-binding protein 1 (ZBP1), and interferon lambda 1 (IFNL1), also referred to as IL-29. Given their responsiveness to IFN signaling, ISG15 and its downstream targets, including MX1 156 , have been implicated as key participants during SARS-CoV-2 infection by using in vitro and in vivo models [157][158][159] as well as samples from COVID-19 patients [160][161][162] . Similarly, the induction of IFNL1 by SARS-CoV-2 infection was previously reported in vitro 163 .…”

Discovery of Initial SARS-CoV-2 as DNA Viruses and Reliable Interactive COVID-19 DNA Methylation Markers and Druggable Targets and Potential Malignant Diseases with Long Incubation Period

“…Solving S4 classifiers (4), we get Table 8 as follows. We note that PARP9 was linked to SARS-CoV-1 and MERS-CoV in the literature [18][19][20]35,36]. It has also been extensively studied its connection to SARS-CoV-2 [37][38][39][40].…”