Essential contribution of the JAK/STAT pathway to carcinogenesis, lytic infection of herpesviruses and pathogenesis of COVID‑19 (Review)

Abstract

The intracellular pathway of Janus kinase/signal transducer and activator of transcription (JAK/STAT) and modification of nucleosome histone marks regulate the expression of proinflammatory mediators, playing an essential role in carcinogenesis, antiviral immunity and the interaction of host proteins with Herpesviral particles. The pathway has also been suggested to play a vital role in the clinical course of the acute infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2; known as coronavirus infection-2019), a novel human coronavirus initially identified in the central Chinese city Wuhan towards the end of 2019, which evolved into a pandemic affecting nearly two million people worldwide. The infection mainly manifests as fever, cough, myalgia and pulmonary involvement, while it also attacks multiple viscera, such as the liver. The pathogenesis is characterized by a cytokine storm, with an overproduction of proinflammatory mediators. Innate and adaptive host immunity against the viral pathogen is exerted by various effectors and is regulated by different signaling pathways notably the JAK/STAT. The elucidation of the underlying mechanism of the regulation of mediating factors expressed in the viral infection would assist diagnosis and antiviral targeting therapy, which will help overcome the infection caused by SARS-CoV-2.

The Possible Role of Pathogens and Chronic Immune Stimulation in the Development of Diffuse Large B-Cell Lymphoma

“…There are several different STATs (STAT1–STAT6) and three JAKs (JAK1, JAK2, JAK3). Upon activation, the phosphorylated STATs form homodimers and heterodimers and translocate to the nucleus, where they interact with other transcriptional factors and regulate the cell proliferation/apoptosis mechanisms, maintaining or suppressing the constant proliferation of the B-cells [ 14 ]. This can lead to B-cell activation or an induction of apoptosis.…”

“…This negatively impacts the immune system, making way for possible B-cell malignancies. The constant activation of the JAK/STAT-signaling pathway has been documented in patients with the SARS-CoV-2 infection, which may also contribute to malignant B-cell evolution [ 14 ]. These pathogenetic events will likely cause lymphoma, but the reported data cannot fully support this hypothesis.…”