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

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.

Retroviruses; HIV; HTLV-1; HERVs; Interferon-γ; Immune regulation

Authorship

Patrícia Azevedo Soares Cordeiro

Universidade de São Paulo , Faculdade de Medicina , Instituto de Medicina Tropical de São Paulo , Laboratório de Investigação em Dermatologia e Imunodeficiências (LIM-56), São Paulo , São Paulo , Brazil Universidade de São PauloBrazilSão Paulo, São Paulo, Brazil Universidade de São Paulo , Faculdade de Medicina , Instituto de Medicina Tropical de São Paulo , Laboratório de Investigação em Dermatologia e Imunodeficiências (LIM-56), São Paulo , São Paulo , Brazil

* These authors contributed equally to this study

https://orcid.org/0000-0002-0300-2648

Tatiane Assone

* These authors contributed equally to this study

https://orcid.org/0000-0003-0993-4523

Gabriela Prates

* These authors contributed equally to this study

https://orcid.org/0000-0003-3728-9621

Marcia Regina Martinez Tedeschi

https://orcid.org/0000-0002-8817-9089

Luiz Augusto Marcondes Fonseca

https://orcid.org/0000-0002-6731-1810

Jorge Casseb

https://orcid.org/0000-0002-4553-2559

Correspondence to: Tatiane Assone Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical de São Paulo, Laboratório de Investigação em Dermatologia e Imunodeficiências (LIM-56), Av. Dr. Enéas de Carvalho Aguiar 500, 3º andar, Prédio 2, CEP 05403-000, São Paulo, SP, Brazil Tel: +55 11 30617194 Fax: +55 11 30817190 E-mail: tatianeassone@usp.br

*
These authors contributed equally to this study

SCIMAGO INSTITUTIONS RANKINGS

Figures

Figures (3)

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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.

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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.

Thumbnail

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.

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 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 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.

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

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[1] Correspondence to: Tatiane Assone Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical de São Paulo, Laboratório de Investigação em Dermatologia e Imunodeficiências (LIM-56), Av. Dr. Enéas de Carvalho Aguiar 500, 3º andar, Prédio 2, CEP 05403-000, São Paulo, SP, Brazil Tel: +55 11 30617194 Fax: +55 11 30817190 E-mail: tatianeassone@usp.br