Background: Lymphocytic choriomeningitis virus (LCMV) infection in immunocompromised hosts can result in disseminated disease, meningoencephalitis, and death. Published cases in transplant recipients have been traced to transmission from infected donors. We report 2 cases of serious, non-donor-derived LCMV infection in solid organ transplant recipients.
Methods: Initial identification of LCMV infection was done by using metagenomic next-generation sequencing (mNGS). Subsequent evaluations and confirmatory testing involved molecular diagnostics, serology, and phylogenetic analysis. A detailed epidemiologic investigation was conducted.
Results: LCMV was detected by mNGS in 2 solid organ transplant recipients from distinct donors. A heart transplant recipient (from donor 1) died of progressive, disseminated LCMV infection, while a kidney transplant recipient (from donor 2) with LCMV meningoencephalitis survived. A multistate laboratory and epidemiologic investigation of both donors and all their organ recipients was initiated. Postmortem samples were obtained from both donors, and pretransplant and/or posttransplant samples were obtained from 5 of the 6 organ recipients. mNGS, serologic, and real-time reverse-transcription polymerase chain reaction testing confirmed LCMV infection in both solid organ transplant recipients. Epidemiologic investigation revealed significant pretransplant rodent exposures for both LCMV-infected recipients. Laboratory studies for the other organ recipients from both donors were negative for LCMV infection.
Conclusions: Our investigations suggest that LCMV infection in 2 solid organ transplant recipients originated from rodent exposure preceding transplantation and were not donor derived. Although uncommon, healthcare providers should be aware of LCMV-associated serious and life-threatening illness in immunocompromised hosts. Diagnostic modalities are limited to reference laboratories.
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http://dx.doi.org/10.1093/ofid/ofaf002 | DOI Listing |
Nat Immunol
March 2025
Shanghai Key Laboratory of Lung Inflammation and Injury, Zhongshan Hospital, Fudan University, Shanghai, China.
Following activation, naive T cells exit quiescence and require global translation for rapid expansion, yet the underlying mechanisms remain unclear. Here, we show that during T cell activation, cells upregulate the expression of N-acetyltransferase 10 (NAT10), an enzyme responsible for N-acetylcytidine (acC) modification of mRNAs. acC-modified Myc mRNAs show higher translation efficiency, enabling rapid synthesis of MYC protein and supporting robust T cell expansion.
View Article and Find Full Text PDFJ Med Virol
March 2025
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
The lymphocytic choriomeningitis virus (LCMV) is a widespread pathogen that causes mild-to-severe infections to severe outcomes. In this study, we explored the potential of trametinib, a mitogen-activated protein kinase (MAPK) inhibitor, as an antiviral agent against LCMV. Trametinib demonstrated significant antiviral activity against two distinct LCMV strains, Armstrong and Cl13, with promising half-maximal inhibitory concentrations (IC) and selectivity indices (SI) indicating its potency and safety profile.
View Article and Find Full Text PDFAntiviral Res
February 2025
Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA. Electronic address:
Lymphocytic choriomeningitis virus (LCMV) can cause severe, life-threatening infection and disease in organ transplant recipients and other immunocompromised individuals. Additionally, significant developmental and neurological disabilities, vision impairments, and miscarriages can occur as a direct result of LCMV infection during pregnancy. Currently, there are no approved antiviral drugs to protect at-risk populations.
View Article and Find Full Text PDFFront Immunol
February 2025
Medical Research Center, Chongqing General Hospital, Chongqing University, Chongqing, China.
Exhaustion of the immune system's ability to adapt to novelty suggests that the changes it undergoes might be a consequence of an evolutionary unpredictable antigenic exposure over a lifetime. Thus, we raise the question of whether a naive immune system can manage new antigens better than an educated immune system. Here, by employing the naive immune system of germ-free (GF) mice without a history of microbial exposure, we compared their adaptive immune responses with those of the conventional (Conv) mice upon new viral infection.
View Article and Find Full Text PDFbioRxiv
February 2025
Department of Pathology, Stanford University, Stanford, CA, USA.
Immune checkpoint blockade can facilitate tumor clearance by T cells, resulting in long term patient survival. However, the capacity of exhausted CD8 T cells (Tex), present during chronic antigen exposure, to form memory after antigen clearance remains unclear. Here, we performed longitudinal single cell RNA/T cell receptor sequencing and ATAC-sequencing on antigen-specific T cells after the clearance of chronic lymphocytic choriomeningitis virus (LCMV) infection.
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