TAM Receptors Are Not Required for Zika Virus Infection in Mice
Andrew K Hastings1, Laura J Yockey2, Brett W Jagger3
1Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
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.
Insights
Tyrosine kinase receptors (TAM) are not essential for Zika virus (ZIKV) infection in mice. Studies show ZIKV can replicate in mice lacking TAM receptors, regardless of the infection route.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Zika virus (ZIKV) is an emerging flavivirus with significant public health implications.
- Tyro3, Axl, and Mertk (TAM) receptors are investigated as potential entry points for ZIKV.
- Understanding ZIKV entry mechanisms is crucial for developing antiviral strategies.
Purpose of the Study:
- To determine if TAM receptors are necessary for ZIKV infection and replication in mice.
- To assess the role of TAM receptors across different ZIKV inoculation routes and mouse models.
Main Methods:
- Utilized wild-type and genetically modified mice lacking specific TAM receptors (Axl, Mertk, Tyro3).
- Infected mice via various routes including subcutaneous, intravaginal, intracranial, and intraperitoneal.
- Administered interferon-alpha-receptor (IFNAR)-blocking antibodies in some experimental groups.
- Quantified viral replication and assessed cell tropism in different organs.
Main Results:
- ZIKV replicated effectively in mice lacking TAM receptors across multiple inoculation routes.
- Interferon-alpha-receptor (IFNAR)-blocking did not alter the lack of reliance on TAMs for infection.
- No significant differences in viral titers or cell tropism were observed in TAM-deficient mice compared to wild-type.
Conclusions:
- TAM receptors are not required for ZIKV entry or infection in mice.
- ZIKV infection and replication can occur independently of TAM receptor expression in vivo.
- These findings suggest alternative pathways for ZIKV entry in the absence of TAM receptors.
