TAM Receptors Are Not Required for Zika Virus Infection in Mice

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Axl Receptor Tyrosine Kinase
  • Female
  • Fetus / virology
  • Injections, Intraperitoneal
  • Mice
  • Placenta / virology
  • Pregnancy
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Tropism
  • Vagina / virology
  • Virus Replication
  • Zika Virus / physiology*
  • Zika Virus Infection / metabolism*
  • c-Mer Tyrosine Kinase

Substances

  • Proto-Oncogene Proteins
  • Mertk protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • Tyro3 protein, mouse
  • c-Mer Tyrosine Kinase
  • Axl Receptor Tyrosine Kinase