Global Transcriptome Analyses of Cellular and Viral mRNAs during HAdV-C5 Infection Highlight New Aspects of Viral mRNA Biogenesis and Cytoplasmic Viral mRNA Accumulations

Viruses. 2022 Nov 1;14(11):2428. doi: 10.3390/v14112428.


It is well established that human adenoviruses such as species C, types 2 and 5 (HAdV-C2 and HAdV-C5), induce a nearly complete shutoff of host-cell protein synthesis in the infected cell, simultaneously directing very efficient production of viral proteins. Such preferential expression of viral over cellular genes is thought to be controlled by selective nucleocytoplasmic export and translation of viral mRNA. While detailed knowledge of the regulatory mechanisms responsible for the translation of viral mRNA is available, the viral or cellular mechanisms of mRNA biogenesis are not completely understood. To identify parameters that control the differential export of viral and cellular mRNAs, we performed global transcriptome analyses (RNAseq) and monitored temporal nucleocytoplasmic partitioning of viral and cellular mRNAs during HAdV-C5 infection of A549 cells. Our analyses confirmed previously reported features of the viral mRNA expression program, as a clear shift in viral early to late mRNA accumulation was observed upon transition from the early to the late phase of viral replication. The progression into the late phase of infection, however, did not result in abrogation of cellular mRNA export; rather, viral late mRNAs outnumbered viral early and most cellular mRNAs by several orders of magnitude during the late phase, revealing that viral late mRNAs are not selectively exported but outcompete cellular mRNA biogenesis.

Keywords: human adenovirus; mRNA biogenesis; mRNA export; next-generation sequencing (NGS); nucleocytoplasmic RNA transport; temporal expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Human* / genetics
  • Adenoviruses, Human* / metabolism
  • Gene Expression Profiling
  • Humans
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Viral Proteins / genetics
  • Virus Replication


  • RNA, Messenger
  • Viral Proteins
  • RNA, Viral

Grants and funding

The LIV is supported by the Freie und Hansestadt Hamburg and the German Bundes-ministerium für Gesundheit (BMG). M.V.A. received funding from the DAAD-CONACYT scholarship program during her PhD. R.A.G. received funds from CONACyT (A1-S-8696) and the RGLP from the Alexander von Humboldt Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.