TAM receptors are not required for Zika virus infection in mice

Summary

Tyro3, Axl and Mertk (TAM) receptors are candidate entry receptor for infection of Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we employed several routes of viral inoculation and compared viral replication in wild-type vs. 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 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 was observed. These findings indicate that in mice, TAM receptors are not required for ZIKV entry and infection.

eTOC Blurb

TAM receptors have been implicated as entry receptors for Zika virus. In this study, Hastings et al. used genetic knockout mouse models to demonstrate that they are not necessary for infection of mice via multiple routes of viral challenge. These results suggest the existence of redundant entry receptors for ZIKV in mice.