Mosquitoes live under the endless threat of infections from different kinds of pathogens such as bacteria, parasites, and viruses. The mosquito defends itself by employing both physical and physiological barriers that resist the entry of the pathogen and the subsequent establishment of the pathogen within the mosquito. However, if the pathogen does gain entry into the insect, the insect mounts a vigorous innate cellular and humoral immune response against the pathogen, thereby limiting the pathogen’s propagation to nonpathogenic levels. This happens through three major mechanisms: phagocytosis, melanization, and lysis. During these processes, various signaling pathways that engage intense mosquito–pathogen interactions are activated. A critical overview of the mosquito immune system and latest information about the interaction between mosquitoes and pathogens are provided in this review. The conserved, innate immune pathways and specific anti-pathogenic strategies in mosquito midgut, hemolymph, salivary gland, and neural tissues for the control of pathogen propagation are discussed in detail.

This study presents a novel plasmonic fiber optic sandwich immunobiosensor for the detection of chikungunya, an infectious mosquito-borne disease with chronic musculoskeletal pain and acute febrile illness, by exploiting non-structural protein 3 (CHIKV-nsP3) as a biomarker. A plasmonic sandwich immunoassay for CHIKV-nsP3 was realized on the surface of a compact U-bent plastic optical fiber (POF, 0.5 mm core diameter) with gold nanoparticles (AuNPs) as labels. The high evanescent wave absorbance (EWA) sensitivity of the U-bent probes allows the absorption of the light passing through the fiber by the AuNP labels, upon the formation of a sandwich immunocomplex of CHIKV-nsP3 on the core surface of the U-bent probe region. A simple optical set-up with a low-cost green LED and a photodetector on either end of the U-bent probe gave rise to a detection limit of 0.52 ng mL⁻¹ (8.6 pM), and a linear range of 1–10⁴ ng mL⁻¹ with a sensitivity of 0.1043A_{530 nm}/log(C_nsP3). In addition, the plasmonic POF biosensor shows strong specificity towards the CHIKV-nsP3 analyte in comparison with Pf-HRP2, HIgG, and dengue whole virus. The results illustrate the potential of plasmonic POF biosensors for direct and sensitive point-of-care detection of the chikungunya viral disease.

Macrophages are efficient reservoirs for viruses that enable the viruses to survive over a longer period of infection. Alphaviruses such as chikungunya virus (CHIKV) are known to persist in macrophages even after the acute febrile phase. The viral particles replicate in macrophages at a very low level over extended period of time and are localized in tissues that are often less accessible by treatment. Comprehensive experimental studies are thus needed to characterize the CHIKV-induced modulation of host genes in these myeloid lineage cells and in one such pursuit, we obtained global transcriptomes of a human macrophage cell line infected with CHIKV, over its early and late timepoints of infection. We analyzed the pathways, especially immune related, perturbed over these timepoints and observed several host factors to be differentially expressed in infected macrophages in a time-dependent manner. We postulate that these pathways may play crucial roles in the persistence of CHIKV in macrophages.

Chikungunya (CHIK) is a febrile arboviral illness caused by chikungunya virus (CHIKV) and has been identified in more than 60 countries across the globe. A major public health concern, the infection occurs as an acute febrile phase and a chronic arthralgic phase. The disease manifests differently in different age groups that can range from asymptomatic infection in the younger age group to a prolonged chronic phase in the elderly population. The present study was undertaken to evaluate strain-specific pathogenesis of ECSA genotype of CHIKV strains derived from clinical isolates in adult C57BL/6J mice model. The strain that was pathogenic and developed distinct acute and post–acute phase of CHIK infection was further evaluated for dose-dependent pathogenesis. Upon arriving on the optimal dose to induce clinical symptoms in the mice, the disease progression was evaluated across the acute and the post–acute phase of infection for a period of 15 days post–infection in two age groups of mice, namely eight weeks old and 20 weeks old mice groups. Biochemical, hematological, and virology attributes were measured and correlated to morbidity and linked neurotropism and limb thickness in the two age groups. Our results show that CHIKV exhibit strain-specific pathogenesis in C57BL/6J mice. Distinct dissimilarities were observed between the two age groups in terms of pathogenesis, viral clearance and host response to CHIKV infection.

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has re-emerged, causing widespread outbreaks and a significant clinical burden. Despite advances in virology, the molecular mechanisms governing CHIKV’s interaction with host cells remain poorly understood. In this study, we aimed to identify novel host protein interactors of the CHIKV nonstructural protein 3 (nsP3), a critical component of the viral replication complex, using mass spectrometry-based proteomic profiling in liver-derived Huh7 cells. Co-immunoprecipitation followed by LC-MS/MS identified a wide array of host proteins associated with nsP3, revealing 52 proteins classified as high-confidence (FDR of 1%, and unique peptides > 2) CHIKV-specific interactors. A bioinformatic analysis using STRING and Cytoscape uncovered interaction networks enriched in metabolic processes, RNA processing, translation regulation, cellular detoxification, stress responses, and immune signaling pathways. A subcellular localization analysis showed that many interactors reside in the cytosol, while others localize to the nucleus, nucleolus, and mitochondria. Selected novel host protein interactions were validated through co-immunoprecipitation and immunofluorescence assays. Our findings provide new insights into the host cellular pathways hijacked by CHIKV and highlight potential targets for therapeutic intervention. This is the first report mapping direct nsP3–host protein interactions in Huh7 cells during CHIKV infection.