# TAM Receptors and Virus Infection

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2020 · $833,577

## Abstract

PROJECT SUMMARY/ABSTRACT
The receptor tyrosine kinases of the TAM family – Tyro3, Axl, and Mer – are essential
regulators of infection by enveloped viruses, and Axl and Mer are especially important to
arbovirus infection of cells of the central nervous system (CNS). Infection of the CNS by
encephalitic arboviruses, including West Nile virus (WNV), often has devastating
consequences, both acutely and after recovery, and deciphering the molecular
mechanisms through which TAM receptors control virus entry, propagation, and
clearance is therefore a key objective. Genetic, molecular biologic, cell biologic, and
behavioral assays will be used to elucidate these mechanisms. In Aim 1, a set of new
conditional mouse mutants and cell-specific Cre drivers will be used to investigate the
CNS cell types through which TAM receptors control infection by WNV and two other
neurotropic enveloped arboviruses - La Crosse encephalitis virus and Venezuelan
equine encephalitis virus. These studies will elucidate the specific roles played by Axl
and Mer in brain microvascular endothelial cells (BMECs), microglia, astrocytes, and
pericytes in neuroinvasion and CNS pathogenesis by these viruses. In Aim 2, a new
mouse model of learning impairment after recovery from CNS infection by WNV will be
used to probe the role that Axl and Mer in microglia and astrocytes play in spatial
learning and memory after infection. These experiments also will assess the role that
cell-specific TAM signaling plays in synapse elimination and neurogenesis subsequent
to WNV infection of the brain. In Aim 3, molecular genetics and cell-based signaling
assays will be used to elucidate the molecular architecture of TAM receptor-Interferon
receptor (IFNAR) interaction, which is crucial to the phenomena of Aims 1 and 2, in
BMECs, microglia, macrophages, and dendritic cells. These studies will identify the
signaling pathways activated by cooperative TAM receptor/INFAR signaling in these
cells, and assess the ability of these interacting receptor systems to reorganize actin
cytoskeletons. Together, the experiments of this proposal will guide the formulation of
novel strategies for inhibiting virus entry into the CNS, attenuating virus infection of
neural cells, and promoting the repair and recovery of infected neural tissues.

## Key facts

- **NIH application ID:** 9815948
- **Project number:** 5R01AI101400-08
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Michael S Diamond
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $833,577
- **Award type:** 5
- **Project period:** 2012-08-21 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815948

## Citation

> US National Institutes of Health, RePORTER application 9815948, TAM Receptors and Virus Infection (5R01AI101400-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9815948. Licensed CC0.

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