Host-Pathogen Interactions in Coronavirus Infections

Coronaviruses engage in a complex interplay with host cells, co-opting cellular machinery to ensure their replication while evading immune detection. Key viral proteins manipulate membrane compartments, notably the endoplasmic reticulum (ER), to form replication organelles that shield viral RNA synthesis from cytosolic sensors. Concurrently, coronaviruses subvert host stress responses and cell‐cycle checkpoints to create a permissive environment for genome amplification. They modulate the unfolded protein response and inhibit translation-shutdown pathways, thus maintaining production of viral proteins. Additionally, accessory and nonstructural proteins interfere with antiviral signalling, including type I interferon pathways and pro-inflammatory transcription factors, dampening innate defences. Viral manipulation of cell‐division regulators leads to S- and G1-phase arrest, optimising nucleotide pools and replication complex assembly. These multifaceted interactions underpin coronavirus pathogenesis, influence disease severity and inform the development of broad-spectrum antiviral strategies.

Research from Nature Portfolio

Pharmacological induction of ER stress has been shown to impose a multi-level blockade on coronavirus replication. Treatment with a small-molecule ER stress inducer restored host translation, counteracted virus-mediated downregulation of key stress sensors and chaperones, and impeded selective autophagy exploited by the virus. Proteome-wide analyses identified host factors of ER quality control and ER-associated degradation that mediate this antiviral state. By simultaneously targeting several essential mechanisms of viral replication, this approach holds promise as a broad-spectrum therapeutic strategy against emerging coronavirus threats.

Host-Pathogen Interactions in Coronavirus Infections publication trend

The graph below shows the total number of articles in host-pathogen interactions in coronavirus infections across all publications each year (not limited to Nature Index journals).

Technical terms

Endoplasmic reticulum (ER) stress: A cellular condition arising from accumulation of unfolded proteins in the ER lumen, triggering adaptive signalling pathways.

Unfolded protein response (UPR): A network of signalling cascades (IRE1α, PERK, ATF6) activated by ER stress to restore proteostasis or initiate apoptosis.

IRE1α–XBP1 axis: One branch of the UPR in which IRE1α mediates unconventional splicing of XBP1 mRNA, yielding a transcription factor that enhances ER folding capacity.

Nonstructural protein (nsp): A virally encoded protein derived from polyprotein processing that fulfils roles in genome replication, transcription and host modulation.

Cell‐cycle arrest: A halt in cell‐division progression, often exploited by viruses to optimise the intracellular environment for replication.

References

1. Coronavirus RNA-dependent RNA polymerase interacts with the p50 regulatory subunit of host DNA polymerase delta and plays a synergistic role with RNA helicase in the induction of DNA damage response and cell cycle arrest in the S phase. Emerging Microbes & Infections (2023).
2. The unfolded protein response components IRE1α and XBP1 promote human coronavirus infection. mBio (2023).
3. Multi-level inhibition of coronavirus replication by chemical ER stress. Nature Communications (2021).