The Role of Cellular Immune Responses on Chikungunya Virus Infection-Induced Arthritis

Versteeg, Leroy; Carter-Febres, Maria; Beaumier, Coreen M.

doi:10.1007/s40475-016-0074-2

Cited by 3 publications

(7 citation statements)

References 48 publications

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“…TNF may promote the activation and proliferation of T cells and thereby regulate the overall T cell mediated effector function (72). In mouse model system, it has been demonstrated that host T cells are induced during experimental CHIKV infection and are associated with CHIKV mediated pathogenesis (43,44,46). In the present study, we found that CHIKV infected macrophage culture supernatant may facilitate TCR driven activation of resting T cells as compared to the mock supernatant.…”

Section: Discussionsupporting

confidence: 51%

“…We and others have previously reported that in vitro CHIKV infection in RAW 264.7 cells leads to TNF production (31,37). Recent studies have shown a pathogenic role of T cells during CHIKV infection associated to host inflammatory responses (43,44,46). Here we have investigated whether CHIKV infection induced macrophage derived TNF can facilitate mouse T cell activation associated with cell mediated immunity.…”

Section: Chikv Induced Tnf Facilitates Tcr Driven T Cell Activationmentioning

confidence: 90%

“…Purified T cells (both CD4 + and CD8 + ) from the chronic and recovered patients from 2005 to 2006 La Reunion islands showed immune activation when challenged with synthetic CHIKV peptides and inactivated virus particles (42). The DNA vaccine based on the consensus sequences of E1/2 and capsid protein (with several modifications) of CHIKV resulted in robust IFN-γ and IgG production suggesting that CHIKV induces both T and B cell specific responses (45,46).…”

Section: Introductionmentioning

confidence: 99%

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P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages

et al. 2019

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Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is endemic in different parts of the globe. The host macrophages are identified as the major cellular reservoirs of CHIKV during infection and this virus triggers robust TNF production in the host macrophages, which might be a key mediator of virus induced inflammation. However, the molecular mechanism underneath TNF induction is not understood yet. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV to address the above-mentioned question. It was observed that CHIKV induces both p38 and JNK phosphorylation in macrophages in a time-dependent manner and p-p38 inhibitor, SB203580 is effective in reducing infection even at lower concentration as compared to the p-JNK inhibitor, SP600125. However, inhibition of p-p38 and p-JNK decreased CHIKV induced TNF production in the host macrophages. Moreover, CHIKV induced macrophage derived TNF was found to facilitate TCR driven T cell activation. Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. Further, it was demonstrated that CHIKV mediated TNF production in the macrophages is dependent on p38 and JNK MAPK pathways linking p-c-jun transcription factor. Interestingly, it was found that CHIKV nsP2 interacts with both p-p38 and p-JNK MAPKs in the macrophages. This observation was supported by the in silico protein-protein docking analysis which illustrates the specific amino acids responsible for the nsP2-MAPKs interactions. A strong polar interaction was predicted between Thr-180 (within the phosphorylation lip) of p38 and Gln-273 of nsP2, whereas, no such polar interaction was predicted for the phosphorylation lip of JNK which indicates the differential roles of p-p38 and p-JNK during CHIKV infection in the host macrophages. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. Hence, this information might shed light in rationale-based drug designing strategies toward a possible control measure of CHIKV infection in future.

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Section: Discussionsupporting

confidence: 51%

Section: Chikv Induced Tnf Facilitates Tcr Driven T Cell Activationmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages

et al. 2019

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“…Numerous CHIKV outbreaks have been reported on almost every continent since the mid-2000s, and they have been identified and confirmed in more than 40 countries. It is estimated that about 2 million people contracted infection by this pathogen in the last 10 years [39]. Currently, chikungunya fever occurs on the Asian continent in: Cambodia, East Timor, India, Indonesia, Laos, Malaysia, Maldives, Myanmar, Pakistan, Philippines, Réunion, Seychelles, Singapore, Taiwan, Thailand and Vietnam; in the African continent: Benin, Burundi, Cameroon, Central African Republic, Comoros, Democratic Republic of Congo, Equatorial Guinea, Guinea, Kenya, Madagascar, Malawi, Mauritius, Mayotte, Nigeria, Senegal, South Africa, Sudan, Tanzania, Uganda and Zimbabwe [40].…”

Section: Epidemiologymentioning

confidence: 99%

“…In addition, a greater number of natural killer cells in peripheral blood have been reported in patients with persistent arthritis caused by chikungunya when compared to healthy individuals [10]. Thus, the evidence indicates that the most severe cases of chikungunya fever depend on multiple factors including viral persistence mechanisms and associated factors such as reactivation of the virus in the joints, of immune response evasion, uncontrolled response for pro-inflammatory cytokine and cross reactivity with autoantigens [7,14,39,107,108].…”

Section: Immune Response Of Hostmentioning

confidence: 99%

Chikungunya fever: a threat to global public health

Moizéis

Fernandes

Guedes

et al. 2018

Pathogens and Global Health

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Chikungunya fever is an emerging arbovirus infection, representing a serious public health problem. Its etiological agent is the Chikungunya virus (CHIKV). Transmission of this virus is mainly vector by mosquitoes of the genus Aedes, although transmission by blood transfusions and vertical transmission has also been reported. The disease presents high morbidity caused mainly by the arthralgia and arthritis generated. Cardiovascular and neurological manifestations have also been reported. The severity of the infection seems to be directly associated with the action of the virus, but also with the decompensation of preexisting comorbidities. Currently, there are no therapeutic products neither vaccines licensed to the infection CHIKV control, although several vaccine candidates are being evaluated and human polyvalent immunoglobulins anti-CHIKV had been tested. Antibodies can protect against the infection, but in sub-neutralizing concentrations can augment virus infection and exacerbate disease severity. So, the prevention still depends on the use of personal protection measures and vector control, which are only minimally effective.

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Immunological impact of cytokines on the chikungunya virus pathophysiology: A literature narrative review

Nunes

Sousa

Smith

et al. 2023

Reviews in Medical Virology

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The chikungunya virus (CHIKV) is a member of the genus Alphavirus, family Togaviridae. CHIKV causes an acute systemic febrile condition, accompanied by severe polyarthralgia, intense muscle pain, and maculopapular exanthema, which may still occur in many patients. In rare cases, unusual symptoms may occur, eventually worsening the condition and resulting in a fatal outcome. It is a single‐stranded, non‐segmented RNA virus with a genome of approximately 11,805 nucleotides that organises a genetic and molecular chain that encodes non‐structural proteins (nsP1, nsP2, nsP3, nsP4) and structural proteins (E3, E2, 6K, and E1). The fundamental role of immune response in the evolution of the disease is known. Understanding the role of immune response in the pathogenesis of CHIKV infection is challenging. In this context, innate and adaptive immune responses establish a connective interface that induces the production of various mediators that modulate the strategy of inhibiting viral replication. However, the immune escape articulated by the virus indicates that the action of pro‐and anti‐inflammatory cytokines contributes to the worsening of the disease and potentiates tissue damage with joint involvement. In this review, we discuss the role of the primary pro‐and anti‐inflammatory cytokines in the immunopathological processes of chikungunya fever.

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The Role of Cellular Immune Responses on Chikungunya Virus Infection-Induced Arthritis

Cited by 3 publications

References 48 publications

P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages

P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages

Chikungunya fever: a threat to global public health

Immunological impact of cytokines on the chikungunya virus pathophysiology: A literature narrative review

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