biostudies-literatureLucas CJNational Institute of Allergy and Infectious DiseasesNIA NIH HHSNIAID NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHSe176537https://www.ebi.ac.uk/biostudies/studies/S-EPMC11143926biostudies-literatureUnknown9(4)Infection with chikungunya virus (CHIKV) causes disruption of draining lymph node (dLN) organization, including paracortical relocalization of B cells, loss of the B cell-T cell border, and lymphocyte depletion that is associated with infiltration of the LN with inflammatory myeloid cells. Here, we found that, during the first 24 hours of infection, CHIKV RNA accumulated in MARCO-expressing lymphatic endothelial cells (LECs) in both the floor and medullary LN sinuses. The accumulation of viral RNA in the LN was associated with a switch to an antiviral and inflammatory gene expression program across LN stromal cells, and this inflammatory response - including recruitment of myeloid cells to the LN - was accelerated by CHIKV-MARCO interactions. As CHIKV infection progressed, both floor and mJCI insightChikungunya virus infection disrupts lymph node lymphatic endothelial cell composition and function via MARCO.PMC11143926R21 AI155929T32 AI052066R01 AI141436R01 AI155474R01 AG071467R01 AI121209R01 AI148144T32 AI074491R35 GM119550McCarthy MKLucas CJDavenport BJHickman HDMorrison TEHesselberth JRTamburini BASheridan RMReynoso GVMartin AfalseChikungunya virus infection disrupts lymph node lymphatic endothelial cell composition and function via MARCO.Infection with chikungunya virus (CHIKV) causes disruption of draining lymph node (dLN) organization, including paracortical relocalization of B cells, loss of the B cell-T cell border, and lymphocyte depletion that is associated with infiltration of the LN with inflammatory myeloid cells. Here, we found that, during the first 24 hours of infection, CHIKV RNA accumulated in MARCO-expressing lymphatic endothelial cells (LECs) in both the floor and medullary LN sinuses. The accumulation of viral RNA in the LN was associated with a switch to an antiviral and inflammatory gene expression program across LN stromal cells, and this inflammatory response - including recruitment of myeloid cells to the LN - was accelerated by CHIKV-MARCO interactions. As CHIKV infection progressed, both floor and m2024-01-01T00:00:00Z2024 Jan2026-06-02T02:13:50.826Z2026-04-13T03:12:51.7ZS-EPMC111439263819426810.1172/jci.insight.176537