# Suppression of KIF3A function by herpes simplex virus-1 US3 kinase for immune evasion

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $247,500

## Abstract

Abstract:
Herpesvirus infection is a major public health problem. Herpes Simplex virus-1 (HSV-1) is the
prototype member of alpha-herpesvirus family. In additional to causing high morbidity and mortality in
oral and neuronal infection in humans, HSV-1 is the leading etiological agent for infection-caused
ocular keratitis and blindness for humans. To establish infection and escape critical components of
the immune systems to remain latent in host cells, HSV-1 has evolved sophisticated immune evasion
strategies. CD1d-restricted innate-like NKT cells play critical anti-microbial functions against different
pathogens, including viruses, bacteria, fungi, and parasites. However, it remains unclear how HSV-1
evades the potent anti-microbial functions of NKT cells during infection and latency. We have
discovered that HSV-1 rapidly and efficiently down-regulates CD1d from the surface of antigen-
presenting cells. US3 is the primary viral gene responsible for this immune evasion function. Through
phosphorylation, the US3 kinase targets the major cellular motor protein, KIF3A to inhibit the
retrograde endosmal trafficking that mediates CD1d recycling to cell surface. We have identified three
new phosphorylation sites in KIF3A by US3 kinase. We will delineate the molecular function of each
phosphorylation event in suppressing the folding, assembly, and motor function of KIF3A to rapidly
shut down KIF3A-mediated transport and inhibit CD1d surface expression. Successful outcome of
this proposal will significantly impact our understanding of herpesvirus-mediated immune evasion as
well as provides novel insights for functional mechanism of key motor protein KIF3A and its
importance in immune evasion of CD1d.

## Key facts

- **NIH application ID:** 9877478
- **Project number:** 1R21AI149365-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Weiming Yuan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,500
- **Award type:** 1
- **Project period:** 2020-01-08 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877478

## Citation

> US National Institutes of Health, RePORTER application 9877478, Suppression of KIF3A function by herpes simplex virus-1 US3 kinase for immune evasion (1R21AI149365-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9877478. Licensed CC0.

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