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Review
. 2022 Sep 30:64:e64.
doi: 10.1590/S1678-9946202264064. eCollection 2022.

The role of IFN-γ production during retroviral infections: an important cytokine involved in chronic inflammation and pathogenesis

Patrícia Azevedo Soares Cordeiro  1 , Tatiane Assone  1 , Gabriela Prates  1 , Marcia Regina Martinez Tedeschi  1 , Luiz Augusto Marcondes Fonseca  1 , Jorge Casseb  1
Affiliations
Review

The role of IFN-γ production during retroviral infections: an important cytokine involved in chronic inflammation and pathogenesis

Patrícia Azevedo Soares Cordeiro et al. Rev Inst Med Trop Sao Paulo. .

Abstract

Interferon-gamma (IFN-γ) plays a crucial role in viral infections by preventing viral replication and in the promotion of innate and adaptive immune responses. However, IFN-gamma can exert distinct effects in different persistent viral infections. The long-term overproduction of IFN-γ in retroviral infections, such as the human immunodeficiency virus (HIV), human T-lymphotropic virus type 1 (HTLV-1), and human endogenous retroviruses (HERVs), resulting in inflammation, may cause neuronal damage. This review is provocative about the role of IFN-γ during persistent retroviral infections and its relationship with the causation of some neurological disorders that are important for public health.

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Figures

Figure 1
Figure 1. Hypothesis of neuroinflammation process during HTLV-1 infection: 1) Activation of inflammation process; 2) T-cell proliferation; 3) Migratory process of infected T cells; 4) Pro-inflammatory cytokines and chemokines secreted during the neurodegeneration process. This inflammatory process will induce the release of cytokines in the spinal cord (thoracic segment). Initially, there is a proinflammatory local involvement, driven mainly due to IFN-gamma. Over a few years, this process is ongoing and chronic with the outcome being degenerative damage to the myelin membrane.
Figure 2
Figure 2. Role of IFN secretion during HIV-1 infection. The presence of HIV RNA in endosomes activates Toll-like receptors, thus activating the NF-kappa beta pathway. The production of IFN-gamma promotes the JAK-STAT activation and consequently signalization of interferon-stimulated genes. After that, antiviral factors such as APOBEC, and TRIM-5alpha are produced.
Figure 3
Figure 3. Endogenous retrovirus expression in the central nervous system. The HERVs are expressed in several cell types. In astrocytes, regarding the viral chronic infection context, there is a major expression of the HERV proteins that, when added with inflammatory molecules, promote neuronal damage.
See this image and copyright information in PMC

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