Lymphocytic choriomeningitis virus (LCMV) isLymphocytic choriomeningitis virus (LCMV) is a prototypic arenavirus with bisegmented single-stranded RNA genome. Both segments (small [S] and large [L]) contain two open reading frames in mutually opposite orientations and utilize an ambisense coding strategy (19). The S RNA encodes a major viral protein nucleoprotein (NP) and a glycoprotein precursor (GP-C), which is cotranslationally cleaved into peripheral glycoprotein 1 (GP1) and transmembrane glycoprotein 2 (GP2) (30). The L RNA segment encodes an RNA-dependent RNA polymerase (L) and a regulatory ring finger Z protein (ZP) (2, 26). Virus replication starts with the L polymerase-driven transcription of the 3Ј RNA genome arms of negative polarity and produces mRNAs that are subsequently translated to NP and L polymerase. These viral proteins assist in the transcription of the RNA genome to virus cRNA, serving as a template for the synthesis of the new genomic RNA molecules as well as for the subgenomic mRNAs translated to GP-C and ZP (2, 19). This unusual two-stage replication strategy facilitates establishment of virus persistence, which can be sustained by the virus ribonucleoprotein composed of NP, the RNA genome, and L polymerase in the absence of mature virion production caused by absent or limited expression of glycoproteins (2, 33). LCMV can easily set up persistent infection in a wide variety of cell types derived from various species, where it does not perturb vital cell functions but modulates nonessential phenotypic features (20,22,33).In vivo, LCMV readily causes persistent infection of common house mouse (Mus musculus), its natural host and reservoir. Humans are generally infected through the respiratory tract after direct or indirect contact with infected rodents or pets. In immunocompetent individuals, LCMV causes illnesses varying from mild flu-like symptoms to rare severe encephalitis (15,22). Infection with this virus during pregnancy has been linked to spontaneous abortions and malformations (16). More strikingly, fatal cases of LCMV infections transmitted via transplanted organs from infected donors to immunosuppressed recipients were recently reported and call for more attention to this seemingly innocent virus (1, 7).The MX strain of LCMV was originally identified in the human MaTu cell line, which was presumably derived from a mammary tumor as described earlier (21,25). Analysis of the MX LCMV coding regions has revealed sequence differences supporting the view that MX is a separate LCMV strain (9,25,32). MX LCMV does not cause any cellular damage, and its host range is restricted to only few cell lines. It is transmissible by direct cell-to-cell contact or cell extract but not by filtered medium of infected cells (25). Furthermore, cells infected with MX LCMV accumulate high cytoplasmic levels of NP and ZP and contain deleted RNAs (9,25,32).Despite NP being the most abundant viral protein expressed in persistently infected cells and a major component of the minimal infection unit of the vir...