# Characterization of Human Cytomegalovirus (HCMV) Long Non-Coding RNA1.2 During Lytic Replication

## TL;DR

This study investigates the role of HCMV RNA1.2 during viral replication and finds it is not essential for replication but may influence host processes.

## Contribution

The study characterizes the function of HCMV RNA1.2 by generating deletion mutants and identifying RNA1.2-associated proteins.

## Key findings

- RNA1.2 deletion mutants showed no defects in viral DNA synthesis, transcript expression, protein production, or progeny generation.
- LC-MS identified RNA1.2-associated cellular proteins involved in innate immunity, mitochondrial processes, and cell cycle regulation.
- RNA1.2 is not essential for lytic replication but may modulate host responses.

## Abstract

During lytic replication of human cytomegalovirus (HCMV), the most abundant viral transcripts are long non-coding RNAs (lncRNAs). Viral lncRNAs can have a variety of functions, some of which are necessary for viral production and the modulation of host processes during infection. HCMV produces four lncRNAs, Beta2.7 (RNA2.7), RNA4.9, RNA5.0 and RNA1.2. While there has been research on these viral lncRNAs, many of their functions remain uncharacterized. To determine the function of RNA1.2, we explored its requirement during lytic infection by generating viral mutants containing either a full or partial deletion of the RNA1.2 locus. Within permissive fibroblasts, the RNA1.2 deletion mutants showed no defects in viral DNA synthesis, transcript expression, protein production, or generation of viral progeny. Further investigation to identify potential cellular and viral protein binding partners of RNA1.2 was performed using liquid chromatography-mass spectrometry (LC-MS). A significant number of cellular proteins were identified and associated with RNA1.2. Specifically those associated with the innate immune response, mitochondrial processes, and cell cycle regulation. While RNA1.2 is dispensable for lytic replication, these findings suggest it may play a pivotal role in modulating the host response.