IFITM Proteins Mediate the Innate Immune Response to Influenza A H1N1 Virus, West Nile Virus and Dengue Virus

By A. Brass, I-Chueh Huang, Yair Benita, S. John, Manoj N. Krishnan, E. Feeley, B. Ryan, J. Weyer, L. Weyden, E. Fikrig and 4 more. Cell, 2009

1,289 citations recorded by the source corpus.

Summary Influenza viruses exploit host cell machinery to replicate, resulting in epidemics of respiratory illness. In turn, the host expresses anti-viral restriction factors to defend against infection. To find host-cell modifiers of influenza A H1N1 viral infection, we used a functional genomic screen and identified over 120 influenza A virus-dependency factors with roles in endosomal acidification, vesicular trafficking, mitochondrial metabolism and RNA splicing. We discovered that the interferon-inducible trans-membrane proteins, IFITM1, 2 and 3, restrict an early step in influenza A viral replication. The IFITM proteins confer basal resistance to influenza A virus, but are also inducible by interferons type I and II, and are critical for interferon's virustatic actions. Further characterization revealed that the IFITM proteins inhibit the early replication of flaviviruses, including dengue virus and West Nile virus. Collectively this work identifies a new family of anti-viral restriction factors that mediate cellular resistance to at least three major human pathogens.

Subfields: Epidemiology, Immunology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/38b51dd8bae5027949cdb9d86250ad11a4e0ad96

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In Epidemiology

1. A. García‐Sastre
2. Charles M. Rice

In Immunology

1. A. García‐Sastre
2. Charles M. Rice
3. Nir Hacohen
4. Stephen J. Elledge

Citations in the corpus

• Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus (2011, methodology): “As we have previously reported [1], infection mediated by the entry proteins of MLV or MACV was unaffected by the presence of IFITM proteins (Fig.”
• Interferon-Stimulated Genes: A Complex Web of Host Defenses (2014, background): “These proteins were recently shown to be potent inhibitors of influenza A virus infection in a loss-of-function screen (143).”
• Interferon-Inducible Cholesterol-25-Hydroxylase Broadly Inhibits Viral Entry by Production of 25-Hydroxycholesterol (2012, background): “The previously described entry inhibitor, Ifitm3, also reduced VSV-G/βlaM fusion (Brass et al., 2009).”
• Meta- and Orthogonal Integration of Influenza “OMICs” Data Defines a Role for UBR4 in Virus Budding (2015, methodology): “…in data analysis methodologies and hit selection, we considered an expanded version of the respective hit lists based on the raw data of previously unpublished activity scores of four genome-wide RNAi screens (Brass et al., 2009; Karlas et al., 2010; König et al., 2010; Ward et al., 2012).”
• SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies (2021, neutral): “Further, we cloned the coding sequence for human ACE2 into the pQCXIP plasmid (Brass et al., 2009), yielding pQCXIP_ACE2.”
• Dengue and severe dengue (2025, neutral): “Secreted type-I IFN then functions in an autocrine or paracrine manner to induce interferon-stimulated genes (ISGs), such as interferon-induced transmembrane protein 1 (IFITM1), to inhibit DENV infection (70).”