The antiviral restriction factors IFITM1, 2 and 3 do not inhibit infection of human papillomavirus, cytomegalovirus and adenovirus.
Type I interferons (IFN-α and β) induce dynamic host defense mechanisms to inhibit viral infections. It has been recently recognized that the interferon-inducible transmembrane proteins (IFITM) 1, 2 and 3 can block entry of a broad spectrum of RNA viruses. However, no study to date has focused on the role of IFITM proteins in DNA virus restriction. Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. However, IFITM1, 2 and 3 overexpression did not inhibit HPV16 infection; rather, IFITM1 and IFITM3 modestly enhanced HPV16 infection in various cell types including primary keratinocytes. Moreover, IFITM1, 2 and 3 did not inhibit infection by two other DNA viruses, human cytomegalovirus (HCMV) and adenovirus type 5 (Ad5). Taken together, we reveal that the entry of several DNA viruses, including HPV, HCMV, and Ad5 is not affected by IFITM1, 2 and 3 expression. These results imply that HPV, and other DNA viruses, may bypass IFITM restriction during intracellular trafficking.
Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Cody J
CJ
Warren
Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Laura M
LM
Griffin
Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Alexander S
AS
Little
Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America.
I-Chueh
IC
Huang
Department of Infectious Diseases, The Scripps Research Institute, Jupiter, Florida, United States of America.
Michael
M
Farzan
Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Dohun
D
Pyeon
D000256:Adenoviridae / Q000276:immunology*; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000276:immunology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*
D000943:Antigens, Differentiation; C080081:IFITM2 protein, human; C080082:IFITM3 protein, human; D016898:Interferon-alpha; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C062010:leu-13 antigen; D016899:Interferon-beta