Sorn, S. | Search bioRxiv

bioRxiv2026

Early Immune Hypoactivation and Persistent Innate Reprogramming Characterize Chronic Chikungunya Disease

Chikungunya virus (CHIKV) infection causes acute febrile illness and debilitating arthralgia, with up to 40-80% of patients developing chronic chikungunya disease characterized by persistent arthralgia and fatigue lasting months to years. The immunological mechanisms underlying this transition remain poorly understood. We performed longitudinal immune profiling of CHIKV-infected patients stratified by clinical outcome. Single-cell RNA sequencing of peripheral blood mononuclear cells collected during acute infection and six months post-infection was combined with multiplex plasma cytokine and flow cytometric analysis. Patients who later developed chronic symptoms were characterized by early innate immune hypoactivation during acute infection, characterized by reduced monocyte and dendritic cell frequencies, lower circulating IFN-, IL-6 and IL-8, and reduced antigen-presentation and interferon-associated transcriptional programs. This was accompanied by diminished adaptive immune activation, including reduced IL-17 and IL-21 and lower HLA-DR expression across multiple T-cell subsets. Cell-cell communication analysis further indicated impaired acute monocyte-centered immune coordination in chronic progressors, whereas non-chronic patients displayed stronger monocyte-driven innate-to-adaptive signaling. By six months, chronic patients showed persistent innate remodeling, including increased non-classical monocytes, altered plasmacytoid dendritic cell and natural killer cell transcriptional programs, elevated CXCL10, reduced IL-6 and MMP8, and emergence of NK-centered predicted communication networks. Longitudinal transcriptomic analysis further identified divergent immune recovery trajectories, most prominently in non-classical monocytes and plasmacytoid dendritic cells. Together, these findings suggest that chronic chikungunya disease is associated with early innate immune hypoactivation followed by persistent innate immune remodeling, providing insight into immune mechanisms that may contribute to post-viral chronic inflammatory syndromes.

immunology↗

bioRxiv2023

The genomic landscape of swine influenza A viruses in Southeast Asia

Swine are a primary source for the emergence of pandemic influenza A viruses. The intensification of swine production, along with global trade, has amplified the transmission and zoonotic risk of swine influenza virus (swIAV). Effective surveillance is essential to uncover emerging virus strains, however gaps remain in our understanding of the swIAV genomic landscape in Southeast Asia. By collecting more than 4,000 nasal swabs and 4,000 sera from pigs in Cambodia, we unmasked the co-circulation of multiple lineages of genetically diverse swIAV of pandemic concern. Genomic analyses revealed a novel European avian-like H1N2 swine reassortant variant with North American triple reassortant internal genes, that emerged approximately seven years before its first detection in pigs in 2021. Using phylogeographic reconstruction, we identified south central China as the dominant source of swine viruses disseminated to other regions in China and Southeast Asia. We also identified nine distinct swIAV lineages in Cambodia, which diverged from their closest ancestors between two to 15 years ago, indicating significant undetected diversity in the region, including reverse zoonoses of human H1N1/2009 pandemic and H3N2 viruses. A similar period of cryptic circulation of swIAVs occurred in the decades before the H1N1/2009 pandemic. The hidden diversity of swIAV observed here further emphasizes the complex underlying evolutionary processes present in this region, reinforcing the importance of genomic surveillance at the human-swine interface for early warning of disease emergence to avoid future pandemics.

microbiology↗