Human cytomegalovirus harnesses host L1 retrotransposon for efficient replication
Genetic parasites, including viruses and transposons, exploit components from the host for their own replication. However, little is known about virus-transposon interactions within host cells. Here, we discover a strategy where human cytomegalovirus (HCMV) hijacks L1 retrotransposon encoded protein during its replication cycle. HCMV infection upregulates L1 expression by enhancing both the expression of L1-activating transcription factors, YY1 and RUNX3, and the chromatin accessibility of L1 promoter regions. Increased L1 expression, in turn, promotes HCMV replicative fitness. Affinity proteomics reveals UL44, HCMV DNA polymerase subunit, as the most abundant viral binding protein of the L1 ribonucleoprotein (RNP) complex. UL44 directly interacts with L1 ORF2p, inducing DNA damage responses in replicating HCMV compartments. While increased L1-induced mutagenesis is not observed in HCMV for genetic adaptation, the interplay between UL44 and ORF2p accelerates viral DNA replication by alleviating replication stress. Our findings shed light on how HCMV exploits host retrotransposons for enhanced viral fitness.
Authors
- Danielle Denisko (ORCID: https://orcid.org/0000-0002-8544-0026)
- Junhyun Park (ORCID: https://orcid.org/0000-0003-1366-0238)
- Dohoon Lee (ORCID: https://orcid.org/0000-0003-2163-5489)
- Eunjung Alice Lee (ORCID: https://orcid.org/0000-0002-6574-9261)
- Jiseok Jeong (ORCID: https://orcid.org/0009-0002-9778-1087)
- Se-Hong Park (ORCID: https://orcid.org/0000-0003-1240-0434)
- Sung-Yeon Hwang (ORCID: https://orcid.org/0000-0001-8342-4690)
- Boxun Zhao (ORCID: https://orcid.org/0000-0003-2337-5756)
- Hee‐Jung Choi (ORCID: https://orcid.org/0000-0002-1167-1526)
- Sun Kim (ORCID: https://orcid.org/0000-0001-5385-9546)
- Hyewon Kim (ORCID: https://orcid.org/0000-0002-9692-6283)
- Jin‐Uk Kim (ORCID: https://orcid.org/0000-0001-9892-9915)
- Dongjoon Jeong
- Kwangseog Ahn (ORCID: https://orcid.org/0000-0002-1015-245X)
- Kiwon Park (ORCID: https://orcid.org/0000-0003-3576-5380)
Institutions
- Broad Institute (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- Seoul National University (KR)
- Institute for Basic Science (KR)
- National University College (PR)
- Boston Children's Museum (US)
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-02
- DOI
- https://doi.org/10.1038/s41467-024-51961-y
- Citations
- 5
- Primary Topic
- Cytomegalovirus and herpesvirus research
- Type
- article
- Field-Weighted Citation Impact
- 1.93
Funders
- Princeton University
- National Research Foundation
- National Research Foundation of Korea
- Tsinghua University
- Institute for Basic Science
- National Institutes of Health
- Manton Center for Orphan Disease Research, Boston Children's Hospital