The Two Sides of the Same Coin—Influenza Virus and Intracellular Signal Transduction

Abstract

Cells respond to extracellular agents by activation of intracellular signaling pathways. Viruses can be regarded as such agents, leading to a firework of signaling inside the cell, primarily induced by pathogen-associated molecular patterns (PAMPs) that provoke safeguard mechanisms to defend from the invader. In the constant arms race between pathogen and cellular defense, viruses not only have evolved mechanisms to suppress or misuse supposedly antiviral signaling processes for their own benefit but also actively induce signaling to promote replication. This creates viral dependencies that may be exploited for novel strategies of antiviral intervention. Here, we will summarize the current knowledge of activation and function of influenza virus-induced signaling pathways with a focus on nuclear factor (NF)-κB signaling, mitogen-activated protein kinase cascades, and the phosphatidylinositol-3-kinase pathway. We will discuss the opportunities and drawbacks of targeting these signaling pathways for antiviral intervention.

Comparing Influenza Virus Biology for Understanding Influenza D Virus

“…In the human host, IAVs continue to cause significant morbidity and mortality each year, while IDVs have not been associated with clinical illness. Long before antibodies that are highly specific for a given pathogen can be produced, many early signals of the innate immune response serve as the first line of defense against infection [ 33 , 34 , 35 ]. Activation of this highly specialized attack system with multiple levels of protection, communication, and functionality involves two critical antiviral pathways that are activated within hours of a viral infection: the interferon regulatory factor (IRF) pathway and the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway [ 33 , 34 ].…”

“…Long before antibodies that are highly specific for a given pathogen can be produced, many early signals of the innate immune response serve as the first line of defense against infection [ 33 , 34 , 35 ]. Activation of this highly specialized attack system with multiple levels of protection, communication, and functionality involves two critical antiviral pathways that are activated within hours of a viral infection: the interferon regulatory factor (IRF) pathway and the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway [ 33 , 34 ]. The IRF and NFκB pathways induce cytokine expression from host cells, and these cytokines act as key communicators of the immune response [ 34 , 35 , 36 ].…”

Cellular Protein Phosphatase 2A Regulates Cell Survival Mechanisms in Influenza A Virus Infection

“…Influenza A viruses (IAVs) evoke annually occurring outbreaks of the common flu, which leads to huge economic losses and hundreds of thousands of deaths worldwide. Due to a very limited genome capacity, IAVs hijack host cellular pathways to facilitate their replication and efficiently inhibit antiviral immune responses (reviewed in [1][2][3]). Several studies were able to correlate this ability with dynamic posttranslational modifications (PTMs) of viral as well as cellular targets (reviewed in [4][5][6]).…”

The local anaesthetic procaine prodrugs ProcCluster® and Procaine-hydrochloride impair SARS-CoV-2 replication in vitro

“…A few studies further indicate antiviral potential of the substance against different viruses [6,7], others report regulatory functions on cellular factors, such as G protein-coupled receptors (GPR) [8], and the mitogenactivated protein kinases (MAPK) [9]. Notably, GPRs and MAPKs mediate virus-induced antiviral cellular functions, but are also used by viruses for own purposes to ensure efficient replication [10,11].…”