<i>Viperin</i> controls chikungunya virus–specific pathogenic T cell IFNγ Th1 stimulation in mice

Carissimo, Guillaume; Teo, Teck‐Hui; Chan, Yi‐Hao; Lee, Cheryl Yi‐Pin; Lee, Bernett; Torres‐Ruesta, Anthony; Tan, Jeslin J. L.; Chua, Tze-Kwang; Fong, Siew‐Wai; Lum, Fok‐Moon; Ng, Lisa F. P.

doi:10.26508/lsa.201900298

Cited by 26 publications

(31 citation statements)

References 56 publications

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“…Pathogenic CHIKV-specific CD4 + T cells in CHIKV mouse models express T-bet and secrete IFN-γ, markers that are associated with Th1 phenotype (50). These findings concur with another study, which shows higher levels of Th1associated cytokines in the sera of CHIKV-infected patients (34).…”

Section: Introductionsupporting

confidence: 87%

Role of T Cells in Chikungunya Virus Infection and Utilizing Their Potential in Anti-Viral Immunity

Poh

Chan

2020

Front. Immunol.

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Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes hallmark debilitating polyarthralgia, fever, and rash in patients. T cell-mediated immunity, especially CD4 + T cells, are known to participate in the pathogenic role of CHIKV immunopathology. The other T cell subsets, notably CD8 + , NKT, and gamma-delta (γδ) T cells, can also contribute to protective immunity, but their effect is not actuated during the natural course of infection. This review serves to consolidate and discuss the multifaceted roles of these T cell subsets during acute and chronic phases of CHIKV infection, and highlight gaps in the current literature. Importantly, the unique characteristics of skin-resident memory T cells are outlined to propose novel prophylactic strategies that utilize their properties to provide adequate, lasting protection.

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Section: Introductionsupporting

confidence: 87%

Role of T Cells in Chikungunya Virus Infection and Utilizing Their Potential in Anti-Viral Immunity

Poh

Chan

2020

Front. Immunol.

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“…repeatedly implicated as important promoters of CHIKV-mediated arthritis 80,[132][133][134][135][136] . Furthermore, regulatory T cells can ameliorate chikungunya arthropathy in mice 137 and are also associated with disease resolution in humans 134 .…”

Section: Cd4 T Cells Chikv-specific Cd4 T Cells Have Beenmentioning

confidence: 99%

“…Furthermore, regulatory T cells can ameliorate chikungunya arthropathy in mice 137 and are also associated with disease resolution in humans 134 . In mouse models of chikungunya, CD4 T cells infiltrated into the joints in a CXC-chemokine receptor 3 (CXCR3)-dependent fashion 80 , with arthritogenic CD4 T cells seeming to have a dominant type 1 T helper (T H 1) cell phenotype 135 , expressing the transcription factor T-bet 104 and IFNγ 32,90,101 . Notably, IFNγexpressing cells are also present in synovial biopsy samples from patients with RRV disease 114 .…”

Section: Cd4 T Cells Chikv-specific Cd4 T Cells Have Beenmentioning

confidence: 99%

“…Conceivably, rather than being reliant on IFNγ, CHIKV-specific T H 1 cells could activate monocytes and macrophages via interactions involving CD28 and CD80-CD86 136,141 , resulting in TNF and IL-6 production 142 . Alternatively, instead of IFNγ expression by T H 1 cells, TNF expression by CD4 cells might have an important function in promoting chikungunya arthropathy 135 . TNF-expressing CD4 cells have a potential pathogenic function in psoriatic arthritis 143 and are targeted by methotrexate in RA 144,145 ; notably, methotrexate has shown some benefit in treating chikungunya 146,147 .…”

Section: Cd4 T Cells Chikv-specific Cd4 T Cells Have Beenmentioning

confidence: 99%

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Rheumatic manifestations of chikungunya: emerging concepts and interventions

2019

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Chikungunya virus (CHIKV) is a member of a group of globally distributed, mosquito-transmitted arthritogenic alphaviruses that cause sporadic outbreaks of primarily rheumatic disease every 2-50 years 1-4. The largest epidemic of CHIKV disease (hereafter simply referred to as chikungunya) ever recorded began on Lamu Island, Kenya, in 2004 (Fig. 1). The epidemic expanded across four continents, with cases still being reported in 2019 (Fig. 1; Supplementary Table 1). Three major genotypes of CHIKV are now recognized-the Asian, the West African and the Asian and East-Central South African (ECSA) genotypes 5-but a new lineage, the Indian Ocean Lineage (IOL), also emerged from the ECSA genotype during the 2004-2019 epidemic 6. The epidemic reached >100 countries (Supplementary Table 1), caused >10 million cases (Supplementary Table 2), and might arguably be called a pandemic. An estimated 1.3 billion people are at risk of chikungunya 7. Climate change modelling suggests that many more areas of the world (including parts of China, sub-Saharan Africa, South America and the United States) might become able to accommodate transmission of CHIKV in the future 8,9. Chikungunya was previously often viewed as (and for many patients remains) a relatively benign and selflimiting rheumatic disease. However, a considerably more complex spectrum of less common atypical and severe manifestations is now recognized in subgroups of patients, with chikungunya often complicated by comorbidities and co-infections. Hospitalization rates for chikun gunya range from 0.6% to 13% 10-14 and estimates of chikungunya-related mortality range from 0.024% to 0.7% 10,12,15-17. In addition, many patients develop protracted rheumatic disease lasting many months, occasionally years, with a number of sequelae now also recognized 18-22. Estimates for the total economic costs (direct and indirect) of chikungunya have ranged from a median of US$67 for adults and $258 for children in Columbia 23 , to a mean of $150 per outpatient and $3,300 per inpatient in 2006 in Réunion Island 11. In a large study of a chikungunya outbreak in Bangladesh in 2017, >10 days of productivity were lost in ~30% of patients with chikung unya because of severe arthropathy 24. Such costs might be viewed as relatively modest by Western standards; however, the occasionally high attack rate of chikungunya, with up to 30-75% of a given population affected by chikungunya disease at any one time 1,25 , can result in a substantial economic burden, especially in resource-poor communities that are often affected by the disease 26. Considerable research in patients and animal models has now provided extensive insights into the complex Pandemic An epidemic of disease that has spread across a large region; for instance, multiple continents, or even worldwide. Attack rate The total number of new cases of a disease divided by the total population (that is, the percentage of a defined population that is affected by a disease).

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“…Among the viruses documented to induce viperin are DNA viruses such as cytomegalovirus (CMV) (7,48,49) and retroviruses such as HIV-1 (45). Viperin also restricts many positive-strand RNA viruses such as flaviviruses, including hepatitis C virus (HCV) (9,12,13), West Nile virus (15), Zika virus (18,21,22), and dengue fever virus (15,16), and alphaviruses that cause Sindbis (25,26) and Chikungunya fevers (23,24,26). Last, viperin exhibits antiviral properties against negative-strand RNA viruses, including orthomyxoviruses such as influenza A virus (11), rhabdoviruses including rabies virus (1,39), and paramyxoviruses such as Sendai virus (1,27).…”

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confidence: 99%

Viperin: An ancient radical SAM enzyme finds its place in modern cellular metabolism and innate immunity

Ghosh

Marsh

2020

Journal of Biological Chemistry

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Viperin plays an important and multifaceted role in the innate immune response to viral infection. Viperin is also notable as one of very few radical SAM-dependent enzymes present in higher animals; however, the enzyme appears broadly conserved across all kingdoms of life, which suggests that it represents an ancient defense mechanism against viral infections. Although viperin was discovered some 20 years ago, only recently was the enzyme’s structure determined and its catalytic activity elucidated. The enzyme converts CTP to 3’,4’-didehydro-3’-deoxy-CTP, which functions as novel chain-terminating antiviral nucleotide when misincorporated by viral RNA-dependent RNA polymerases. Moreover, in higher animals, viperin interacts with numerous other host and viral proteins, and it is apparent that this complex network of interactions constitutes another important aspect of the protein’s antiviral activity. An emerging theme is that viperin appears to facilitate ubiquitin-dependent proteasomal degradation of some of the proteins it interacts with. Viperin- targeted protein degradation contributes to the antiviral response either by down-regulating various metabolic pathways important for viral replication or by directly targeting viral proteins for degradation. Here, we review recent advances in our understanding of the structure and catalytic activity of viperin, together with studies investigating the interactions between viperin and its target proteins. These studies have provided detailed insights into the biochemical processes underpinning this unusual enzyme’s wide-ranging antiviral activity. We also highlight recent intriguing reports that implicate a broader role for viperin in regulating non-pathological cellular processes, including thermogenesis and protein secretion.

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Viperin controls chikungunya virus–specific pathogenic T cell IFNγ Th1 stimulation in mice

Abstract: This study shows that Viperin controls the microenvironment pro-inflammatory response and CD4 T cell–mediated pathogenesis during anti-chikungunya virus immune response in mice.

Cited by 26 publications

References 56 publications

Role of T Cells in Chikungunya Virus Infection and Utilizing Their Potential in Anti-Viral Immunity

Role of T Cells in Chikungunya Virus Infection and Utilizing Their Potential in Anti-Viral Immunity

Rheumatic manifestations of chikungunya: emerging concepts and interventions

Viperin: An ancient radical SAM enzyme finds its place in modern cellular metabolism and innate immunity

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