IFITM Proteins Incorporated into HIV-1 Virions Impair Viral Fusion and Spread

Alex A. Compton, Timothée Bruel, Françoise Porrot, Adeline Mallet, Martin Sachse,

Marine Euvrard, Chen Liang, Nicoletta Casartelli, and Olivier Schwartz.

Cell Host & Microbe, 2014. 16, 736-747

Speaker: Yu-Rou Liao (廖毓柔)                          Time: 13:00~14:00, Mar. 11, 2015

Commentator: Dr. Shainn-Wei Wang (王憲威老師)  Place: Room 601

Abstract:

Interferon-inducible transmembrane (IFITM) proteins are membrane-bound restricition factors that inhibit the entry of several viruses including type 1 human immunodeficiency virus (HIV-1)¹. IFITM proteins were proved to block the infection of cell-free HIV-1 in uninfected target cells². However, the authors found that the antiviral activity of IFITM proteins in target cells was overcomed during HIV-1 cell-to-cell transmission. To elucidate whether IFITM proteins exert other antiviral functions during HIV-1 cell-to-cell transmission, they modified the coculture system in which IFITM3 expression was induced either in virus-producing donor cells, in target cells, or in both. By detecting the Gag signal in target cells, they found that IFITM3 in donor cells decreases HIV-1 transmission, and the inhibition is more obvious when both donor and target cells expressing IFITM3. The authors further explored the impact of IFITM3 on infected cells. Western blot analysis revealed that IFITM3 is present in the membrane of viral particles releasing from IFITM3-positive cells. They further found that the increasing amounts of IFITM3 incorporated into virions contribute to the decrease of virus infectivity. Moreover, the authors investigated the mechanism by which IFITM3 in donor cells limits virion infectivity. Since IFITM proteins block viral entry at the stage of fusion, they hypothesized that IFITM3 in virions would have similar functions. Virion fusion assay disclosed that the fusion of IFITM3-containing virion is significantly declined. Immunofluorescence analysis further revealed that IFITM proteins colocalize with viral Env and Gag proteins where virus budding probably takes place. In conclusion, these results show that IFITM3 localized to the viral membrane restricts HIV-1 entry into new target cells by blocking virus-cell fusion. In the present study, the authors revealed a distinct antiviral function of IFITM proteins in HIV-1 virion during cell-to-cell transmission, which provides us a better understanding of how IFITM proteins restrict HIV-1 infection.

References:

1         Perreira, J. M. et al. IFITMs restrict the replication of multiple pathogenic viruses. J. Mol. Biol., 2013. 425, 4937-4955.

2          Lu, J. et al. The IFITM proteins inhibit HIV-1 infection. J. Virol., 2011. 85, 2126-2137.