Chemokines, small molecules crucial in cell interaction, play a pivotal role during viral infections. In viral infections, chemokines are released, connecting components to enhance innate and adaptive immune responses, and promoting cell migration to infection sites. However, viruses employ molecular mimicry to evade the immune system. Understanding chemokine dynamics is crucial for comprehending immune responses and developing therapeutic strategies against viral infections.
Related Products
Introduction of CXCL10
CXCL10, an IFN-induced angiostatic CXC chemokine, binds CXCR3 present in various immune cells. In inflammatory states, CXCL10 is secreted by immune cells, epithelial cells, and fibroblasts. Lacking the anti-angiogenic ELR motif, CXCL10's gene is on chromosome 4 at q21, producing a 12 kDa protein with disulfide cross-bridges. Its structure, a typical chemokine fold, includes a β sheet and α helix with receptor binding residues. Transcription is induced by cytokines and bacterial components, regulated by NF-κB and ISRE. CXCL10 is implicated in infectious diseases, autoimmune conditions, and cancer, exacerbating inflammation and causing tissue damage. Expressing within tissues post-viral infections, CXCL10 plays a crucial role in host defense, activating lymphocytes and facilitating their migration to infection sites.
The Multifaceted Role of CXCL10 in Viral Infections
CXCL10, a chemokine, plays a multifaceted role in various viral infections, particularly those caused by RNA and DNA viruses, as well as oncolytic viruses. Its impact during RNA viral infections is intricate and contingent on the specific context. CXCL10 demonstrates a protective function in certain infections, contributing to viral clearance and fostering a robust T cell response. Notably, in the case of murine hepatitis virus (MHV) infection, the absence of CXCL10 results in elevated viral titers and diminished T cell infiltration in the brain, leading to heightened mortality. In other scenarios like dengue virus infection, CXCL10 impedes viral entry and replication. Nevertheless, in diseases such as HIV, heightened levels of CXCL10 are correlated with increased virus replication.
In RNA viral respiratory syndromes, such as SARS-CoV-2 (COVID-19), there is a significant elevation in CXCL10 levels closely tied to disease severity. CXCL10 not only contributes to lung pathology but also shows a correlation with disease outcomes, indicating its potential as a biomarker. The intricate interplay among CXCL10, interleukin-6 (IL-6), and macrophages within the lungs during COVID-19 highlights its role in cytokine storms and the advancement of the disease.
In DNA viral infections, CXCL10 maintains its versatility by playing various roles. It actively engages in innate antiviral defense against viruses like vaccinia and varicella-zoster, recruiting and activating immune cells. In the context of hepatitis B virus (HBV) infection, heightened levels of CXCL10 are linked to increased disease severity and liver damage. Notably, in herpes simplex virus type 1 (HSV-1) infection, CXCL10 assumes a crucial role in mobilizing CD8+ T cells, contributing to immunity against recurrent herpes. Conversely, in herpes simplex virus type 2 (HSV-2) infection, CXCL10 fosters viral replication.
Fig. 1 Role of CXCL10 during DNA viral infections (Elemam N. M., et al. 2022).
CXCL10 also plays a pivotal role in oncolytic viruses, as its expression is triggered within tumors. Introducing CXCL10 into oncolytic viruses amplifies their effectiveness against tumors by fostering the infiltration of immune cells into the tumor microenvironment.
To sum up, the functions of CXCL10 are intricate and contingent on the specific context in viral infections, influencing aspects such as viral clearance, immune response, and disease outcomes. A comprehensive understanding of these complexities is essential for devising targeted therapeutic approaches and exploring CXCL10's potential as a biomarker in diverse viral infections.
References
- Elemam N. M.; et al.CXCL10 chemokine: A critical player in RNA and DNA viral infections. Viruses. 2022, 14(11): 2445.
- Liu M.; et al. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine & Growth Factor Reviews. 2011, 22(3): 121-130.
.
