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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900091v1 183/6/3569    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Moltedo, B. Articles by Moran, T. M. PubMed PubMed Citation Articles by Moltedo, B. Articles by Moran, T. M.

Cutting Edge: Stealth Influenza Virus Replication Precedes the Initiation of Adaptive Immunity¹

Bruno Moltedo^*, Carolina B. López^*, Michael Pazos^*, María Inés Becker^,, Tamar Hermesh^* and Thomas M. Moran^2,*

^* Department of Microbiology and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029; Biosonda Corp., Santiago, Chile, and Fundación Ciencia y Tecnología para el Desarrollo, Santiago, Chile

A timely immune response is crucial for the effective control of virus infection. The influenza virus NS1 protein interferes with the expression of key proinflammatory cytokines from infected cells in vitro. To investigate the effect of NS1 during the onset of immunity in vivo, we systematically studied the early events that occur in the lungs and draining lymph nodes upon infection with influenza virus. Strikingly, no sign of innate immunity was detected in the lungs for almost 2 days after infection until a sudden inflammatory burst, including IFNs, cytokines, and chemokines, occurred. This burst preceded the robust dendritic cell migration and T cell activation in the lymph nodes. An NS1-deficient virus triggered rapid inflammation in the lungs whereas a wild-type virus did not. Thus, we demonstrate that, in vivo, influenza virus uses the NS1 protein to replicate for almost 2 days after infection before detection by the immune system.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants R01 AI41111 and R21 AI077007 (to T.M.M.). M.I.B was supported by Fondo Nacional de Desarrollo Científico y Tecnológico Grant 1050150.

² Address correspondence and reprint requests to Dr. Thomas M. Moran, Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029. E-mail address: thomas.moran{at}mssm.edu

³ Abbreviations used in this paper: DC, dendritic cell; BM, bone marrow; dpi, days postinfection; hpi, hours postinfection; MLN, mediastinal lymph node; NDV, Newcastle disease virus; qPCR, quantitative RT-PCR; SeV, Sendai virus; SeV-C, SeV Cantell; CCH, concholepas hemocyanin; C-488, CCH labeled with Alexa Fluor 488; NS1, nonstructural protein 1; -NS1, absence of NS1.

⁴ The online version of this article contains supplemental material.