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Cell Host Microbe. 2014 Dec 10;16(6):736-47. doi: 10.1016/j.chom.2014.11.001. Epub 2014 Nov 26.

IFITM proteins incorporated into HIV-1 virions impair viral fusion and spread.

Author information

1
Institut Pasteur, Department of Virology, Virus & Immunity Unit, Paris 75015, France; CNRS URA 3015, Paris 75015, France. Electronic address: alex.compton@pasteur.fr.
2
Institut Pasteur, Department of Virology, Virus & Immunity Unit, Paris 75015, France; CNRS URA 3015, Paris 75015, France.
3
Institut Pasteur, Imagopole, Ultrastructural Microscopy Platform, Paris 75015, France.
4
Institut Pasteur, Department of Virology, Virus & Immunity Unit, Paris 75015, France; École Normale Supérieure, Department of Biology, Cachan 94230, France.
5
Lady Davis Institute, McGill AIDS Centre, Montreal, QC H3T 1E2, Canada.
6
Institut Pasteur, Department of Virology, Virus & Immunity Unit, Paris 75015, France; CNRS URA 3015, Paris 75015, France; Vaccine Research Institute, Creteil 94010, France. Electronic address: schwartz@pasteur.fr.

Abstract

The interferon-induced transmembrane (IFITM) proteins protect cells from diverse virus infections by inhibiting virus-cell fusion. IFITM proteins also inhibit HIV-1 replication through mechanisms only partially understood. We show that when expressed in uninfected lymphocytes, IFITM proteins exert protective effects during cell-free virus infection, but this restriction can be overcome upon HIV-1 cell-to-cell spread. However, when present in virus-producing lymphocytes, IFITM proteins colocalize with viral Env and Gag proteins and incorporate into nascent HIV-1 virions to limit entry into new target cells. IFITM in viral membranes is associated with impaired virion fusion, offering additional and more potent defense against virus spread. Thus, IFITM proteins act additively in both productively infected cells and uninfected target cells to inhibit HIV-1 spread, potentially conferring these proteins with greater breadth and potency against enveloped viruses.

PMID:
25464829
DOI:
10.1016/j.chom.2014.11.001
[Indexed for MEDLINE]
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