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In this study, we have mapped the regions and specific amino acid residues within NP involved in its anti-IFN activity. We identified a region spanning residues 382 to 386 as playing a critical role in the IFN-counteracting activity of NP. Alanine substitutions at several positions within this region resulted in NP mutants that lacked the IFN-counteracting activity but retained their functions in virus RNA synthesis and assembly of infectious particles. We used reverse genetics to rescue a recombinant LCMV strain carrying mutation D382A in its NP [rLCMV\/NP*(D382A)]. Compared to wild-type (WT) LCMV, rLCMV\/NP*(D382A) exhibited a higher level of attenuation in IFN-competent than IFN-deficient cells. In addition, A549 cells infected with rLCMV\/NP*(D382A), but not with WT LCMV, produced IFN and failed to rescue replication of the IFN-sensitive Newcastle disease virus.<\/jats:p>","DOI":"10.1128\/jvi.00763-09","type":"journal-article","created":{"date-parts":[[2009,8,27]],"date-time":"2009-08-27T00:50:20Z","timestamp":1251334220000},"page":"11330-11340","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":129,"title":["Identification of Amino Acid Residues Critical for the Anti-Interferon Activity of the Nucleoprotein of the Prototypic Arenavirus Lymphocytic Choriomeningitis Virus"],"prefix":"10.1128","volume":"83","author":[{"given":"Luis","family":"Marti\u0301nez-Sobrido","sequence":"first","affiliation":[{"name":"Department of Microbiology"},{"name":"Global Health and Emerging Pathogens Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se\u0301bastien","family":"Emonet","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Giannakas","sequence":"additional","affiliation":[{"name":"Department of Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Cubitt","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"Garci\u0301a-Sastre","sequence":"additional","affiliation":[{"name":"Department of Microbiology"},{"name":"Global Health and Emerging Pathogens Institute"},{"name":"Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, One Gustave L. 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