Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection.
The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. While IFITMs are widely known to inhibit several single-stranded RNA viruses, there are limited reports available regarding their effect in double-stranded DNA viruses. In this work, we have analyzed a possible antiviral function of IFITMs against a double stranded DNA virus, the African swine fever virus (ASFV). Infection with cell-adapted ASFV isolate Ba71V is IFN sensitive and it induces IFITMs expression. Interestingly, high levels of IFITMs caused a collapse of the endosomal pathway to the perinuclear area. Given that ASFV entry is strongly dependent on endocytosis, we investigated whether IFITM expression could impair viral infection. Expression of IFITM1, 2 and 3 reduced virus infectivity in Vero cells, with IFITM2 and IFITM3 having an impact on viral entry/uncoating. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV.
Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain.
Raquel
R
Muñoz-Moreno
Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain.
Miguel Ángel
MÁ
Cuesta-Geijo
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, United States of America.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, United States of America.
Carles
C
Martínez-Romero
Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain.
Lucía
L
Barrado-Gil
Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain.
Inmaculada
I
Galindo
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, United States of America.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, United States of America.|Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America.
Adolfo
A
García-Sastre
Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain.
Covadonga
C
Alonso
D000358:African Swine Fever Virus / Q000472:pathogenicity*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D012328:RNA Viruses / Q000378:metabolism; D012330:RNA, Double-Stranded; D014709:Vero Cells; D053586:Virus Internalization
D000943:Antigens, Differentiation; D008565:Membrane Proteins; D012330:RNA, Double-Stranded; C062010:leu-13 antigen; D007372:Interferons; D002784:Cholesterol