Lassa virus (LASV) is a member of the Old World Complex of arenaviruses infecting an estimated 300,000-500,000 people each year primarily in the endemic region of West Africa. Lassa fever (LF), a neglected tropical disease, puts a heavy burden on the communities in which it is endemic. Reportedly, 15%-20% or up to 50% during epidemics succumb to LASV infection. Without U.S. Food and Drug Administration approved diagnostics, therapeutics, or vaccines, knowledge of this disease must advance in order to create affordable and reliable care. Unlike other viral infections, LF does not stimulate a robust humoral immune response. Many in vitro studies have demonstrated the ability of LASV nucleoprotein (NP) and Z protein to interrupt innate immune activation of important cytokines and costimulatory molecules, which can impair the adaptive immune response. To this end, we investigated the antibody and cytokine responses in LF confirmed patients. We then investigated the role NP plays in subverting the innate immune response, suggesting a possible mechanism for humoral immune impairment. Our findings demonstrate a prolonged IgM response and a dysregulated cytokine response in vivo. Additionally, we show LASV NP is capable of modulating the immune system by masking pathogen pattern signals, namely dsRNA, that initiate immune cascades via the Toll Like Receptor 3 pathway. / 1 / Jessica Nicole Hartnett