In silico prediction of the granzyme B degradome

10.1186/1471-2164-12-S3-S1110th Int. Conference on Bioinformatics - 1st ISCB Asia Joint Conference 2011, InCoB 2011/ISCB-Asia 2011: Computational Biology - Proceedings from Asia Pacific Bioinformatics Network (APBioNet)12SUPPL. 3S1

Fast Tracks and Roadblocks for Zika Vaccines

In early 2014, a relatively obscure virus, the Zika virus, made headlines worldwide following an increase in the number of congenital malformations. Since then, research on Zika virus, treatment and vaccines have progressed swiftly with various drugs being repurposed and vaccines heading into clinical trials. Nonetheless, the need for a vaccine is crucial in order to eradicate this re-emerging arthropod-borne virus which remained silent since its first discovery in 1947. In this review, we focused on how the inconspicuous virus managed to spread, the key immunological factors required for a vaccine and the various vaccine platforms that are currently being studied

SVM-based prediction of linear B-cell epitopes using Bayes Feature Extraction

10.1186/1471-2164-11-S4-S21BMC Genomics11SUPPL. 4S2

Virus infection drives IL-2 antibody complexes into pro-inflammatory agonists in mice

The use of IL-2/JES6-1 Ab complex (IL-2 Ab Cx) has been considered as a potential therapeutic for inflammatory diseases due to its selective expansion of regulatory T cells (Tregs) in mice. Here, IL-2 Ab Cx was explored as a therapeutic agent to reduce joint inflammation induced by chikungunya virus, an alphavirus causing debilitating joint disease globally. Virus-infected mice treated with IL-2 Ab Cx exhibited exacerbated joint inflammation due to infiltration of highly activated CD4(+) effector T cells (Teffs). Virus infection led to upregulation of CD25 on the Teffs, rendering them sensitive towards IL2 Ab Cx. Ready responsiveness of Teffs to IL-2 was further demonstrated in healthy human donors, suggesting that the use of IL-2 Ab Cx in humans is not suitable. Changes in IL-2 sensitivity during active virus infection could change the responsive pattern towards the IL-2 Ab Cx, resulting in the expansion of pro-inflammatory rather than anti-inflammatory responses

Early clearance of Chikungunya virus in children is associated with a strong innate immune response

Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children

Co-infection with Chikungunya virus alters trafficking of pathogenic CD8(+) T cells into the brain and prevents Plasmodium-induced neuropathology

Arboviral diseases have risen significantly over the last 40 years, increasing the risk of co‐infection with other endemic disease such as malaria. However, nothing is known about the impact arboviruses have on the host response toward heterologous pathogens during co‐infection. Here, we investigate the effects of Chikungunya virus (CHIKV ) co‐infection on the susceptibility and severity of malaria infection. Using the Plasmodium berghei ANKA (PbA) experimental cerebral malaria (ECM ) model, we show that concurrent co‐infection induced the most prominent changes in ECM manifestation. Concurrent co‐infection protected mice from ECM mortality without affecting parasite development in the blood. This protection was mediated by the alteration of parasite‐specific CD8+ T‐cell trafficking through an IFN γ‐mediated mechanism. Co‐infection with CHIKV induced higher splenic IFN γ levels that lead to high local levels of CXCL 9 and CXCL 10. This induced retention of CXCR 3‐expressing pathogenic CD8+ T cells in the spleen and prevented their migration to the brain. This then averts all downstream pathogenic events such as parasite sequestration in the brain and disruption of blood–brain barrier that prevents ECM ‐induced mortality in co‐infected mice

Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen

Re-emergence of chikungunya virus, a mosquito-transmitted pathogen, is of serious public health concern. In the past 15 years, after decades of infrequent, sporadic outbreaks, the virus has caused major epidemic outbreaks in Africa, Asia, the Indian Ocean, and more recently the Caribbean and the Americas. Chikungunya virus is mainly transmitted by Aedes aegypti mosquitoes in tropical and subtropical regions, but the potential exists for further spread because of genetic adaptation of the virus to Aedes albopictus, a species that thrives in temperate regions. Chikungunya virus represents a substantial health burden to affected populations, with symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. The inflammatory response coincides with raised levels of immune mediators and infiltration of immune cells into infected joints and surrounding tissues. Animal models have provided insights into disease pathology and immune responses. Although host innate and adaptive responses have a role in viral clearance and protection, they can also contribute to virus-induced immune pathology. Understanding the mechanisms of host immune responses is essential for the development of treatments and vaccines. Inhibitory compounds targeting key inflammatory pathways, as well as attenuated virus vaccines, have shown some success in animal models, including an attenuated vaccine strain based on an isolate from La Reunion incorporating an internal ribosome entry sequence that prevents the virus from infecting mosquitoes and a vaccine based on virus-like particles expressing envelope proteins. However, immune correlates of protection, as well as the safety of prophylactic and therapeutic candidates, are important to consider for their application in chikungunya infections. In this Review, we provide an update on chikungunya virus with regard to its epidemiology, molecular virology, virus-host interactions, immunological responses, animal models, and potential antiviral therapies and vaccines

Safety and potential efficacy of cyclooxygenase-2 inhibitors in coronavirus disease 2019

Objectives While the safety of non‐steroidal anti‐inflammatory drugs in COVID‐19 has been questioned, they may be beneficial given the hyper‐inflammatory immune response associated with severe disease. We aimed to assess the safety and potential efficacy of cyclooxygenase‐2 (COX‐2) selective inhibitors in high‐risk patients. Methods Retrospective study of patients with COVID‐19 pneumonia and aged ≥ 50 years who were admitted to hospital. Adverse outcomes analysed included supplemental oxygen use, intensive care unit admission, mechanical ventilation and mortality, with the primary endpoint a composite of any of these. Plasma levels of inflammatory cytokines and chemokines were measured in a subset. Results Twenty‐two of 168 (13.1%) in the cohort received COX‐2 inhibitors [median duration 3 days, interquartile range (IQR) 3–4.25]. Median age was 61 (IQR 55–67.75), 44.6% were female, and 72.6% had at least one comorbidity. A lower proportion of patients receiving COX‐2 inhibitors met the primary endpoint: 4 (18.2%) versus 57 (39.0%), P = 0.062. This difference was less pronounced after adjusting for baseline difference in age, gender and comorbidities in a multivariate logistic regression model [adjusted odds ratio (AOR) 0.45, 95% CI 0.14–1.46]. The level of interleukin‐6 declined after treatment in five of six (83.3%) treatment group patients [compared to 15 of 28 (53.6%) in the control group] with a greater reduction in absolute IL‐6 levels (P‐value = 0.025). Conclusion Treatment with COX‐2 inhibitors was not associated with an increase in adverse outcomes. Its potential for therapeutic use as an immune modulator warrants further evaluation in a large randomised controlled trial