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Cell Rep. 2017 Apr 18;19(3):558-568. doi: 10.1016/j.celrep.2017.03.058.

TAM Receptors Are Not Required for Zika Virus Infection in Mice.

Author information

1
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
3
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
4
Department of Obstetrics and Gynecology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
5
Department of Obstetrics and Gynecology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
6
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: erol.fikrig@yale.edu.
7
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: diamond@wusm.wustl.edu.
8
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: akiko.iwasaki@yale.edu.

Abstract

Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl-/-, Mertk-/-, Axl-/-Mertk-/-, and Axl-/-Tyro3-/- mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection.

KEYWORDS:

CNS; congenital infection; flavivirus; neurotropic virus; pregnancy; viral entry

PMID:
28423319
PMCID:
PMC5485843
DOI:
10.1016/j.celrep.2017.03.058
[Indexed for MEDLINE]
Free PMC Article

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