Dataset Information

IFITM-Family Proteins: The Cell's First Line of Antiviral Defense.

ABSTRACT: Animal cells use a wide variety of mechanisms to slow or prevent replication of viruses. These mechanisms are usually mediated by antiviral proteins whose expression and activities can be constitutive but are frequently amplified by interferon induction. Among these interferon-stimulated proteins, members of the IFITM (interferon-induced transmembrane) family are unique because they prevent infection before a virus can traverse the lipid bilayer of the cell. At least three human IFITM proteins-IFITM1, IFITM2, and IFITM3-have antiviral activities. These activities limit infection in cultured cells by many viruses, including dengue virus, Ebola virus, influenza A virus, severe acute respiratory syndrome coronavirus, and West Nile virus. Murine Ifitm3 controls influenza A virus infection in vivo, and polymorphisms in human IFITM3 correlate with the severity of both seasonal and highly pathogenic avian influenza virus. Here we review the discovery and characterization of the IFITM proteins, describe the spectrum of their antiviral activities, and discuss potential mechanisms underlying these effects.

SUBMITTER: Bailey CC

PROVIDER: S-EPMC4295558 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IFITM-Family Proteins: The Cell's First Line of Antiviral Defense.

Bailey Charles C CC Zhong Guocai G Huang I-Chueh IC Farzan Michael M

Annual review of virology 20141101

Animal cells use a wide variety of mechanisms to slow or prevent replication of viruses. These mechanisms are usually mediated by antiviral proteins whose expression and activities can be constitutive but are frequently amplified by interferon induction. Among these interferon-stimulated proteins, members of the IFITM (interferon-induced transmembrane) family are unique because they prevent infection before a virus can traverse the lipid bilayer of the cell. At least three human IFITM proteins-I ...[more]

PMID: 25599080

Similar Datasets

Project description:Interferon-inducible transmembrane (IFITM) proteins are small homologous proteins that are encoded by the interferon-stimulated genes (ISGs), which can be strongly induced by interferon (IFN) and provide resistance to invasion by a variety of viral pathogens. However, the exact molecular mechanisms underlying this function have remained elusive. The antiviral activity of IFITMs from different species depends on S-palmitoylation at conserved cysteine residues. However, specific enzymes involved in the dynamic palmitoylation cycle of IFITMs, especially depalmitoylase, have not yet been reported. Here, we demonstrate that α/-hydrolase domain-containing 16A (ABHD16A) is a depalmitoylase and a negative regulator of IFITM protein that can catalyze the depalmitoyl reaction of S-palmitoylated IFITM proteins, thereby decreasing their antiviral activities on RNA viruses. Using the acyl-PEGyl exchange gel shift (APEGS) assay, we identified ABHD16A proteins from humans, pigs, and mice that can directly participate in the palmitoylation/depalmitoylation cycles of IFITMs in the constructed abhd16a-/- cells and ABHD16A-overexpressing cells. Furthermore, we showed that ABHD16A functions as a regulator of subcellular localization of IFITM proteins and is related to the immune system. It is tempting to suggest that pharmacological intervention in IFITMs and ABHD16A can be achieved either through controlling their expression or regulating their activity, thereby providing a broad-spectrum therapeutic strategy for animal viral diseases. IMPORTANCE IFITM protein is the cells first line of antiviral defense that blocks early stages of viral replication; the underlying mechanism might be associated with the proper distribution in cells. The palmitoylation/depalmitoylation cycle can dynamically regulate protein localization, stability, and function. This work is the first one that found the critical enzyme that participates in the palmitoylation/depalmitoylation cycle of IFITM, and this type of palmitoyl loss may be an essential regulation mode for balancing the antiviral functions of the IFN pathway. These findings imply that the pharmacological intervention in IFITM and ABHD16A, either through controlling their expression or regulating their activities, could provide a broad-spectrum therapeutic strategy for animal viral diseases and complications linked to interferon elevation.

Dataset Information

IFITM-Family Proteins: The Cell's First Line of Antiviral Defense.

Publications

IFITM-Family Proteins: The Cell's First Line of Antiviral Defense.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets