# Novel Translational Control Mechanisms in Host Range Restriction of Poxvirus

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $466,746

## Abstract

All viruses rely on host translational machinery for protein synthesis. As such, translation
control constitutes a universal host defense against viruses. A new understanding on how host
regulates translation in response to viral infection and how viruses evade this host response will
provide fundamental insight into viral pathogenesis and benefit the development of new antiviral
strategies.
 Poxviruses include some dangerous emerging pathogens as well as some promising vaccine
vectors. Unlike many other viruses, poxvirus host range is not affected by the entry step but
restricted by intracellular processes. Particularly, cellular translational control pathways have a
profound impact on poxvirus host range, and poxvirus inhibitors of these pathways could
manifest as critical host-range factors. The best-known example is PKR-mediated control of
translation initiation and its antagonism by two vaccinia virus (VACV) host-range proteins E3
and K3. Much less is understood about a PKR-independent pathway targeted by two critical
VACV host-range proteins, K1 and C7. VACV with deletion in both K1 and C7 fails to replicate
in most mammalian cells due to a shut-off of viral and host protein synthesis. Intriguingly, the
translational shut-off is independent of PKR and RNaseL and appears not to involve any
translation initiation factors. A paralogous pair of interferon-stimulated genes, SAMD9 and
SAMD9L (SAMD9&L), were recently identified by us and others as the specific targets of K1
and C7. However, how they regulate protein synthesis and restrict poxvirus host range is
unknown and is the focus of this proposal.
 We have made sustained contributions to the understanding of K1/C7 and their cellular
targets for over a decade, including the determination of the structures of K1/C7 and the
identification of SAMD9L as a cellular target of K1/C7. In addition, we have obtained compelling
preliminary data that led to our novel hypotheses, which will be addressed separately with the
following specific aims.
Aim 1. To determine how SAMD9 is activated to inhibit protein synthesis.
Aim 2. To determine how activated SAMD9 inhibits protein synthesis.
Aim 3. To determine the molecular basis underlying the host species-specific SAMD9&L
inhibition by OPXV inhibitors.

## Key facts

- **NIH application ID:** 10123169
- **Project number:** 1R01AI151638-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Junpeng Deng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $466,746
- **Award type:** 1
- **Project period:** 2020-09-22 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123169

## Citation

> US National Institutes of Health, RePORTER application 10123169, Novel Translational Control Mechanisms in Host Range Restriction of Poxvirus (1R01AI151638-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123169. Licensed CC0.

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