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Biology subjects

Schmidt, H. M.

Publications and source records attributed to Schmidt, H. M..

3 recordsLinked to original sources
bioRxiv2026

Enhanced early IgG-mediated complement deposition in the development of chronic chikungunya virus disease

Chikungunya virus (CHIKV) disease typically resolves following acute infection; however, some individuals develop chronic CHIKV disease (CCD) characterized by persistent, debilitating joint pain. Antibodies help clear CHIKV through neutralization and Fc effector functions. Previous studies have associated CCD with a poor neutralizing antibody response; however, the role of Fc effector functions in CCD development remains unclear. Here, purified IgG from post-acute serum of individuals who either resolved CHIKV disease or developed CCD was evaluated for IgG activity and Fc effector functions to identify correlations with disease progression and biomarkers for CCD. Resolution was associated with higher levels of CHIKV-specific IgG and IgG1 and stronger CHIKV neutralization. Regression analysis identified bulk IgG2 as a strong predictor of CHIKV disease progression. Development of CCD was associated with enhanced IgG-mediated complement deposition on infected cells. These findings suggest that localized complement activation at sites of infection may contribute to persistent inflammation underlying CCD.

immunology↗
bioRxiv2025

UFMylation promotes orthoflavivirus infectious particle production

Post-translational modifications play crucial roles in viral infections, yet many potential modifications remain unexplored in orthoflavivirus biology. Here we demonstrate that the UFMylation system, a post-translational modification system that catalyzes the transfer of UFM1 onto proteins, promotes infection by multiple orthoflaviviruses including dengue virus, Zika virus, West Nile virus, and yellow fever virus. We found that depletion of the UFMylation E3 ligase complex proteins UFL1 and UFBP1, as well as other UFMylation machinery components (UBA5, UFC1, and UFM1), significantly reduces infectious virion production for orthoflaviviruses but not the hepacivirus, hepatitis C. Mechanistically, UFMylation does not regulate viral RNA translation or RNA replication but instead affects a later stage of the viral lifecycle. We identified novel interactions between UFL1, and several viral proteins involved in orthoflavivirus virion assembly, including NS2A, NS2B-NS3, and Capsid. These findings establish UFMylation as a previously unrecognized post-translational modification system that promotes orthoflavivirus infection, likely through modulation of viral assembly. This work expands our understanding of the post-translational modifications that control orthoflavivirus infection and identifies new potential therapeutic targets. ImportanceOrthoflaviviruses depend on host-mediated post-translational modifications to successfully complete their lifecycle, yet many of these critical interactions remain undefined. Here, we describe a role for a post-translational modification pathway, UFMylation, in promoting infectious particle production of ZIKV and DENV. We show that UFMylation regulates these viruses at a lifecycle stage after initial RNA translation and RNA replication. Additionally, we find that regulation of infection by UFMylation extends to other orthoflaviviruses, including West Nile virus and yellow fever virus, but not to the broader Flaviviridae family. Finally, we demonstrate that UFMylation machinery directly interacts with specific DENV and ZIKV proteins during infection. These studies reveal a previously unrecognized role for UFMylation in regulating orthoflavivirus infection.

microbiology↗