# Identification of key circadian rhythm-associated genes as differentially expressed genes for cytomegalovirus infection in very-low-birth-weight infants

**Authors:** Qianqian Li, Ying Liu, Dongmei Chen, Wenjie Yuan, Liu Han, Ting Zu, Junmei Yan

PMC · DOI: 10.7717/peerj.20885 · 2026-03-03

## TL;DR

This study identifies PER1 and CRY1 as key circadian rhythm genes with reduced expression in very-low-birth-weight infants infected with cytomegalovirus.

## Contribution

The study identifies PER1 and CRY1 as novel differentially expressed circadian rhythm genes in HCMV-infected very-low-birth-weight infants.

## Key findings

- PER1 and CRY1 mRNA levels were significantly decreased in HCMV-infected VLBW infants compared to controls.
- The findings suggest PER1 and CRY1 could be potential therapeutic targets for HCMV infection in VLBW infants.

## Abstract

Human cytomegalovirus (HCMV) infection has adverse effects on very low-birth-weight infants (VLBW) and is complicated with liver dysfunction, thrombocytopenia, and hearing impairment. Therefore, we explored new potential intervention targets in VLBW infants with HCMV infection.

Enrichment analysis of adult HCMV infection and control groups was performed in the GSE81246 dataset. Peripheral blood mononuclear cells (PBMCs) from VLBW infants with HCMV and those without HCMV (n = 3 per group) (collection: 9–10 a.m.) were sent for RNA-seq to enrich the transcriptome of the obtained GSE290897 dataset. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways with the same enrichment results and significant changes in the two datasets were selected and analyzed. Then the screened genes were verified using reverse transcription polymerase chain reaction (RT-PCR) and quantitative PCR (qPCR).

The key circadian rhythm genes PER1 and CRY1 were screened. RT-qPCR was used to detect PER1 and CRY1 mRNA levels in the PBMCs of VLBW infants with HCMV (n = 12) and the controls (n = 6) (collection: 9–10 a.m.). And results showed that PER1 and CRY1 mRNA was significantly decreased in HCMV infection than in the controls (P < 0.0001; P < 0.0001).

PER1 and CRY1 mRNA was significantly decreased in PBMCs from HCMV infected VLBW infants, providing new ideas for studying potential effective therapeutic targets for HCMV infection in VLBW infants.

## Linked entities

- **Genes:** PER1 (period circadian regulator 1) [NCBI Gene 5187], CRY1 (cryptochrome circadian regulator 1) [NCBI Gene 1407]
- **Diseases:** cytomegalovirus infection (MONDO:0005132), thrombocytopenia (MONDO:0002049), hearing impairment (MONDO:0005365)

## Full-text entities

- **Genes:** EIF4E (eukaryotic translation initiation factor 4E) [NCBI Gene 1977] {aka AUTS19, CBP, EIF4E1, EIF4EL1, EIF4F, eIF-4E}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CRY1 (cryptochrome circadian regulator 1) [NCBI Gene 1407] {aka DSPD, PHLL1}, CD34 (CD34 molecule) [NCBI Gene 947], PER1 (period circadian regulator 1) [NCBI Gene 5187] {aka PER, RIGUI, hPER}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, NR1D2 (nuclear receptor subfamily 1 group D member 2) [NCBI Gene 9975] {aka BD73, EAR-1R, REVERBB, REVERBbeta, RVR}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, PER2 (period circadian regulator 2) [NCBI Gene 8864] {aka FASPS, FASPS1}, TP53BP1 (tumor protein p53 binding protein 1) [NCBI Gene 7158] {aka 53BP1, TDRD30, p202, p53BP1}, EIF3D (eukaryotic translation initiation factor 3 subunit D) [NCBI Gene 8664] {aka EIF3S7, eIF3-p66, eIF3-zeta}, CD14 (CD14 molecule) [NCBI Gene 929], CLOCK (clock circadian regulator) [NCBI Gene 9575] {aka KAT13D, bHLHe8}, NFIL3 (nuclear factor, interleukin 3 regulated) [NCBI Gene 4783] {aka E4BP4, IL3BP1, NF-IL3A, NFIL3A}, Per1 (period circadian clock 1) [NCBI Gene 18626] {aka Hftm, Per, m-rigui, mPer1}, Cry1 (cryptochrome circadian regulator 1) [NCBI Gene 12952] {aka Phll1}, IL3 (interleukin 3) [NCBI Gene 3562] {aka IL-3, MCGF, MULTI-CSF}, LINC-ROR (long intergenic non-protein coding RNA, regulator of reprogramming) [NCBI Gene 100885779] {aka ROR, lincRNA-RoR, lincRNA-ST8SIA3}, BMAL1 (basic helix-loop-helix ARNT like 1) [NCBI Gene 406] {aka ARNTL, ARNTL1, BMAL1c, JAP3, MOP3, PASD3}, PER3 (period circadian regulator 3) [NCBI Gene 8863] {aka FASPS3, GIG13}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, DBP (D-box binding PAR bZIP transcription factor) [NCBI Gene 1628] {aka DABP, taxREB302}
- **Diseases:** hearing impairment (MESH:D034381), CC (MESH:C566443), metabolic diseases (MESH:D008659), glioblastoma (MESH:D005909), sepsis (MESH:D018805), herpesvirus infection (MESH:D006566), mood disorders (MESH:D019964), autoimmune diseases (MESH:D001327), infectious mononucleosis (MESH:D007244), breast cancer (MESH:D001943), inflammatory bowel diseases (MESH:D015212), CMV infection (MESH:D003586), muscle diseases (MESH:D009135), CCGS (MESH:C536209), liver dysfunction (MESH:D017093), infected (MESH:D007239), cardiovascular diseases (MESH:D002318), thrombocytopenia (MESH:D013921), immune disorders (MESH:D007154), cancer (MESH:D009369), MF (MESH:C567116), HBV infection (MESH:D006509), neurodegenerative diseases (MESH:D019636), sleep disorders (MESH:D012893), carcinogenic (MESH:D011230), viral infections (MESH:D014777), stunted growth (MESH:D006130), atherosclerosis (MESH:D050197)
- **Chemicals:** calcium (MESH:D002118), SYBR Green I (MESH:C098022), Lipid (MESH:D008055), TRIzol (MESH:C411644), 3-methyl-4-nitrophenol (MESH:C008636), PNMC (-), histamine (MESH:D006632), oxygen (MESH:D010100)
- **Species:** Human immunodeficiency virus 1 (no rank) [taxon 11676], Hepatitis B virus (no rank) [taxon 10407], Cytomegalovirus (genus) [taxon 10358], Comamonas testosteroni (species) [taxon 285], Human betaherpesvirus 5 (no rank) [taxon 10359], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], hepatitis C virus [taxon 11103]

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965172/full.md

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Source: https://tomesphere.com/paper/PMC12965172