Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

Futsch, Nicolas; Prates, Gabriela; Mahieux, Renaud; Casseb, Jorge; Dutartre, Hélène

doi:10.3390/v10120691

Cited by 68 publications

(60 citation statements)

References 152 publications

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“…This results in the production of TNF-α, IL-6, interferon (IFN)-g and intrathecal antibody, resulting in consequent destruction of glial tissue and neurons, loss of myelin, and fibrillary gliosis. Aye et al (Aye et al, 2000) reported brain perivascular cells infiltration in HAM/TSP and similar chronic lesions are seen in the spine and in the brain (Saito and Bangham, 2012;Futsch et al, 2018). HAM/TSP patients are characterized by elevated levels of IL-4, IL-6, IL-8, IFNg and TNF-α in their plasma and IFN-g, TNF-α, IL-6, and IL-1β in the CSF (Raulino Goncalves et al, 2017).…”

Section: Discussionmentioning

confidence: 98%

Cognitive impairment in HTLV-1-associated myelopathy, proviral load and inflammatory markers

Champs

Passos

Carvalho

et al. 2019

International Journal of Infectious Diseases

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Objectives: Myelopathy is a well-established long-term clinical manifestation of HTLV-1 infection. Besides motor dysfunction, cognitive impairment may be another consequence of HTLV-1 infection. Moreover, inflammatory markers may be associated with cognitive impairment in these patients. The present study compared the cognitive performance of HAM/TSP patients with healthy controls and investigated the associations between cognitive performance, proviral load and blood inflammatory markers. Methods: Eighty-three patients fulfilling diagnostic criteria for HAM/TSP were submitted to a comprehensive clinical, cognitive and functional evaluation, brain magnetic resonance imaging and determination of levels of IL-1β, IL-6, TNF-α, immunoglobulins and HTLV-1 proviral load in blood and cerebrospinal fluid. The control group was composed of 88 cognitively healthy subjects, matched for age, sex and educational level. Results: Compared to healthy subjects, HAM/TSP patients displayed significant global cognitive impairment and executive function deficits. HAM/TSP cognitive impairment was significantly associated with altered levels of IgM, IgG, IL-6 and TNF-α in blood. There was no association between HAM/TSP cognitive impairment and HTLV-1 proviral load. Conclusions: This study suggests cognitive impairment may be a long-term clinical manifestation of HTLV-1 infection, which seems to be linked to the persistent inflammatory activity that is found in the disease.

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Section: Discussionmentioning

confidence: 98%

Cognitive impairment in HTLV-1-associated myelopathy, proviral load and inflammatory markers

Champs

Passos

Carvalho

et al. 2019

International Journal of Infectious Diseases

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“…Since evidence has shown that Tax inhibits UPF1 enzymatic activity by preventing its association with RNA [119], we can hypothesize that other RNA decay pathways that depend on UPF1 are also likely altered, extending the impact of UPF1 on HTLV-1 deregulation. Notably, RMD plays a critical role in immunity and inflammation with the downregulation of multiple transcripts, such as IL-6, IL-2, IL-1b, TNFR2, CD44, and c-Rel, which are also often characterized in HTLV-1 infection [141,156].…”

Section: Discussionmentioning

confidence: 99%

“…As T cells and infected CD4+ T cells in cerebrospinal fluid and neural tissues. It is characterized by a chronic inflammatory state due to elevated cytokine expression and production (reviewed in [13,141]). We wondered whether NMD downregulation, induced for the early infective stage of HTLV-1, may play a role in the later steps of the infection and could converge with ATL or HAM/TSP onset.…”

Section: Htlv-1-associated Pathologies How Can Nmd Inhibition Impactmentioning

confidence: 99%

An Antiviral Process Targeting HTLV-1: The Complex Relationship between HTLV-1 and Nonsense-mediated mRNA Decay

Prochasson¹,

Jalinot²,

Mocquet³

2020

Preprint

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Before the adaptive immune response is established, retroviruses can be targeted by several cellular host factors at different stages of the viral replication cycle. This intrinsic immunity relies on a large diversity of antiviral processes. In the case of HTLV-1 infection, these active innate host defence mechanisms are debated. Among these mechanisms, we focused on a RNA decay pathway called nonsense-mediated mRNA decay (NMD), which can target multiple viral RNAs, including HTLV-1 unspliced RNA, as it has been recently demonstrated. NMD is a cotranslational process that depends on the RNA helicase UPF1 and regulates the expression of multiple types of host mRNAs. RNA sensitivity to NMD depends on mRNA organization and the ribonucleoprotein (mRNP) composition.HTLV-1 has evolved several means to evade the NMD threat, leading to NMD inhibition. In the early steps of infection, NMD inhibition favours the production of HTLV-1 infectious particles, which may contribute to the survival of the most fit clones despite genome instability; however, its direct longterm impact remains to be investigated.

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“…CXCL9 and CXCL10 induce the recruitment of CXCR3 expressing cells including the CXCR3 + IFN-γ producing HTLV-1 infected CD4 + T cells that promote the production of CXCL10 by the astrocytes, creating a positive feedback loop that results in the CNS chronic inflammation (Futsch et al, 2018). In Multiple Sclerosis (MS), which is also a demyelinating neuroinflammatory disease, it is thought that CXCL9 and CXCL10 in the CSF are involved in the recruitment of CXCR3 + T cells into CNS and contribute to MS pathogenesis (Müller et al, 2010;Cheng and Chen, 2014;Vazirinejad et al, 2014;Koper et al, 2018).…”

Section: Cxcl9 and Cxcl10mentioning

confidence: 99%