Yellow fever virus (YFV), but not mumps virus, infection reduces T-cell receptor signaling in murine splenocytes and reduces protein tyrosine phosphatase receptor epsilon (PTPRE) protein expression in splenocytes, draining lymph nodes, and liver tissues. Mice (C57BL/6; n = 5 per group) were infected with 1 × 106 median tissue culture infective dose (TCID50) YFV or mumps virus intraperitoneally (IP), and sacrificed on the indicated days. Splenocytes were stimulated with anti-CD3 and interleukin 2 (IL-2) release measured (A). IL-2 measurements represent the average of 3 technical replicates and each experiment was independently repeated with consistent results. PTPRE levels relative to actin were measured in splenocytes 7 days postinfection (B), draining lymph nodes (C), and liver tissues (D) by immune blot analyses. *P < .01. Abbreviations: IL-2, interleukin 2; PTPRE, protein tyrosine phosphatase receptor epsilon; YFV, yellow fever virus.