Lymphotropic Viruses: Chronic Inflammation and Induction of Cancers

Abstract

Inflammation induced by transcription factors, including Signal Transducers and Activators of Transcription (STATs) and NF-κB, in response to microbial pathogenic infections and ligand dependent receptors stimulation are critical for controlling infections. However, uncontrolled inflammation induced by these transcription factors could lead to immune dysfunction, persistent infection, inflammatory related diseases and the development of cancers. Although the induction of innate immunity and inflammation in response to viral infection is important to control virus replication, its effects can be modulated by lymphotropic viruses including human T-cell leukemia virus type 1 (HTLV-1), Κaposi’s sarcoma herpesvirus (KSHV), and Epstein Barr virus (EBV) during de novo infection as well as latent infection. These lymphotropic viruses persistently activate JAK-STAT and NF-κB pathways. Long-term STAT and NF-κB activation by these viruses leads to the induction of chronic inflammation, which can support the persistence of these viruses and promote virus-mediated cancers. Here, we review how HTLV-1, KSHV and EBV hijack the function of host cell surface molecules (CSMs), which are involved in the regulation of chronic inflammation, innate and adaptive immune responses, cell death and the restoration of tissue homeostasis. Thus, better understanding of CSMs-mediated chronic activation of STATs and NF-κB pathways in lymphotropic virus-infected cells may pave the way for therapeutic intervention in malignancies caused by lymphotropic viruses.

Potential inhibitors interacting in Neuropilin-1 to develop an adjuvant drug against COVID-19, by molecular docking

“…From dockinǵs result (Tables S2–S12), we determined the main amino acids in NRP1 to interact with the ten compounds, these are Tyr297, Asn300, Trp301, Thr316, Gly318, Glu319, Asp320, Ser321, Arg323, Glu348, Lys351, Tyr353, Trp411, Thr413 and Gly414 for N1 – N10 compounds, and for EG00229 and EG01377 the amino acids: Tyr297, Trp301, Gly318, Asp320, Glu348, Thr349, Lys351, Thr413 and Ile415 ( Table 2 ). It is reported that Asp320 is very important for NRP1 to interact with different ligands and VEGF-A, 29 , 33 as well as for the CendR region in HTLV-1 18, 22 , 23 and the SARS-CoV-2, 17 which is present in the analyzed interactions.…”

“…The neuropilin-1 (NRP1) is a multifunctional protein on the cell membrane, with an impact on physiological functions and diseases in the human organism, 16 , 18 , 19 , 20 , 21 , 22 , 23 for which for more than 20 years specific molecules have been developed that can inhibit/regulate some of its functions, 20 , 24 , 25 , 27 , 28 , 29 , 30 , 31 but they are still developments today and the NRP1 continues to demonstrate new signals/functions, which need further investigation. Therefore, the role of NRP1 in the infectious process of COVID-19 has taken on greater relevance, 16 , 32 since by being able to limit these functions on COVID-19, they could generate a disease with less impact on the human organism and this could help the immune system and being able to alter as it is known today, the natural history of the COVID-19 disease.…”

“…Neuropilin-1 (NRP1) is a transmembrane glycoprotein expressed on the cell surface, multifunctional; NRP1 is present in various physiological processes, has been identified in various signaling and interaction functions with different ligands (as pleiotropic coreceptors), with various diseases including leukemia / adult T -cell lymphoma (ATL), 18 as well as NRP1 works in several steps of the angiogenic cascade (with VEGF ligand binding) 19 , 20 ; to study the above, there are studies that demonstrate the role of NRP1 as a receptor and risk factor for developing viral diseases, such as those caused by the Epstein Barr Virus (EBV) and the Human T -lymphotropic Virus Type-1 (HTLV-1); in which it has been shown how NRP1 interacts directly with EBV, 21 and the NRP1 is a risk factor that favors the entry of EBV into nasopharyngeal epithelial cells (in which this type of cells has more expression of NRP1), as well as the relationship with a CendR interaction region of HTLV-1, which facilitates interaction with NRP1 and favors penetration into cells, 18 , 22 , 23 as well as S1 of SARS-CoV-2 Protein-S, showing that NRP1 can potentiate infection in the presence of other host factors. 16 …”

New Look of EBV LMP1 Signaling Landscape

“…It is also known that LMP1 functions as an inflammation-promoting factor, at least by inducing a panel of pro-inflammatory cytokines, such as TNFα, IL6, IP10, among many others, via NFκB, AP1, and STAT3 [174][175][176]. Activation of NFκB and AP1 by LMP1 also induces miRNAs including miR-155, miR-146a, and miR-21, which play key roles in the regulation of inflammation [177][178][179].…”

Virus Association with Gastric Inflammation and Cancer: An Updated Overview

“…These viruses are generally transmitted by the fecal-oral route and show strong tissue tropism to small intestinal epithelial cells, causing diarrhea [7]. Recent studies demonstrated that some of these enteric viruses, along with gammaherpesvirus members, EBV, may also play an essential role in the induction of gut inflammation leading to cancer [8]. In this comprehensive review, we have thoroughly discussed critical studies and recent scientific updates that link the pathological functions of viruses associated with gastric inflammation and cancer.…”