title: Junin virus infects mouse cells and induces innate immune responses.
abstract: Junín virus is the causative agent for Argentine hemorrhagic fever, and its natural host is the New World rodent Calomys musculinus. The virus is transmitted to humans by aerosolization, and it is believed that many of the clinical symptoms are caused by cytokines produced by sentinel cells of the immune system. Here we used the Junín virus vaccine strain Candid 1 to determine whether mouse cells could be used to study virus entry and antiviral innate immune responses. We show that Candid 1 can infect and propagate in different mouse-derived cell lines through a low-pH-dependent, transferrin receptor 1-independent mechanism, suggesting that there is a second entry receptor. In addition, Candid 1 induced expression of the antiviral cytokines tumor necrosis factor alpha and beta interferon in macrophages, and this induction was independent of viral replication. Using Candid 1, as well as virus-like particles bearing the viral glycoprotein, to infect different primary cells and established macrophage cell lines with deletions in the Toll-like receptor (TLR) pathway, we show that TLR2 is a cellular sensor of both the Parodi and Candid 1 viral glycoproteins. Because Junín virus is highly lethal in humans, the use of an experimentally tractable model system, such as the mouse, could provide a better understanding of the antiviral innate cellular responses to Junín virus and the role of these responses in pathogenesis.
authors: Department of Microbiology and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors: Christian D
authors: CD
authors: Cuevas
authors: Madakasira
authors: M
authors: Lavanya
authors: Enxiu
authors: E
authors: Wang
authors: Susan R
authors: SR
authors: Ross
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D018051:Junin virus / Q000254:growth & development* / Q000276:immunology*; D051379:Mice; D011991:Receptors, Virus / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology; D053586:Virus Internalization
chemical_list: D016207:Cytokines; D011991:Receptors, Virus; D051195:Toll-Like Receptor 2