Journal
CELL REPORTS
Volume 19, Issue 3, Pages 558-568Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.03.058
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Funding
- NIH [R01AI089824, R01 AI073755, R01 AI101400, R01 AI104972, 2R01-AI101400-05, AI054359, R21 AI131284, T32GM007205, 4T32HL007974-15, 2T32GM007067-42, 2T32AI007172-36A1]
- March of Dimes PRI Investigator award [21-FY13-28]
- Moderna
- Sanofi
- Visterra
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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-a-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.
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