# The role of host and viral translation factors during HCMV infection

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $384,607

## Abstract

Abstract
No virus encodes a ribosome, thus all viruses require the host translation machinery for the synthesis of viral
proteins. This fundamental host:pathogen interface creates competition for the host translation machinery,
which is a critical barrier to human cytomegalovirus (HCMV) mRNA translation. Many viruses prevent
competition for the translation machinery by inhibiting host translation, however host translation is maintained
during HCMV infection. How HCMV mRNAs successfully compete for access to host translation machinery to
ensure efficient viral protein synthesis is poorly understood, highlighting a critical gap in our knowledge of the
mechanisms controlling HCMV mRNA translation. How might HCMV mRNAs compete with host mRNAs for
access to ribosomes? Based on our data we hypothesize that HCMV avoids competition by using a unique
complement of host and viral translation initiation factors to facilitate viral mRNA translation. Formation of the
eIF4F translation initiation complex is the limiting step in host mRNA translation, thus competition between host
and viral mRNAs would be most intense for eIF4F components. We showed that the eIF4F complex is
necessary for the continued translation of host mRNAs during infection; however HCMV mRNAs translate
efficiently when the eIF4F complex is disrupted. We found that translation of the HCMV IE1 and IE2 mRNAs,
which encode critical regulators of virus replication, is resistant to eIF4F disruption, depletion or inhibition. How
HCMV mRNAs translate in the absence of eIF4F is unknown. As translation initiation factors assemble on the
mRNA 5' untranslated region (5'UTR), in Aim1 we determine how RNA sequence and structure in the shared
5'UTR of the IE1 and IE2 mRNAs recruit cellular factors to allow for their eIF4F-independent translation. We
also determine how these factors contribute to the widespread eIF4F-independent translation of HCMV
mRNAs as a whole. Aim 2 builds on our published results suggesting that the HCMV TRS1 protein (pTRS1)
acts as a viral translation initiation factor to facilitate viral protein synthesis. While pTRS1 antagonizes the
antiviral kinase PKR, which inhibits protein synthesis, we showed that pTRS1 stimulates translation in PKR
deficient cells. Further, we found that pTRS1 binds the mRNA cap independent of the eIF4F complex and co-
purifies with 40S ribosomal subunits, suggesting a role in translation initiation. We now show that pTRS1
interacts with the DHX29 RNA helicase, a translation initiation factor that can recruit ribosomes to mRNAs in
the absence of the eIF4F complex, and that DHX29 is necessary for efficient IE1/2 mRNA translation and virus
replication. In Aim 2 we role of pTRS1 and DHX29 in translation initiation complex on HCMV mRNAs, and the
role of their interaction in the ability of pTRS1 to enhance translation independent of PKR antagonism. We
further determine how pTRS1 binding to DHX29 impacts virus replication and the translation of HCMV mRNAs
in the...

## Key facts

- **NIH application ID:** 9962275
- **Project number:** 5R01AI103311-08
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Nathaniel J Moorman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $384,607
- **Award type:** 5
- **Project period:** 2012-12-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962275

## Citation

> US National Institutes of Health, RePORTER application 9962275, The role of host and viral translation factors during HCMV infection (5R01AI103311-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9962275. Licensed CC0.

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