Virology

Virology encompasses the study of submicroscopic infectious agents—viruses—that rely on host cells for replication. Viruses possess simple architectures, typically an RNA or DNA genome enclosed in a protein coat and, in many cases, a lipid envelope. They infect all domains of life, subvert cellular machinery and can trigger acute or chronic diseases ranging from self-limiting colds to life-threatening haemorrhagic fevers and cancers. Research spans structural virology, elucidating capsid organisation and genome packaging; molecular virology, uncovering replication strategies and host–virus interactions; immunovirology, exploring immune evasion; and applied virology, advancing antivirals, vaccines and engineered viral vectors. Modern techniques—from high-resolution imaging and single-cell omics to genomics and biophysical modelling—have revealed the dynamic formation of viral replication factories, the role of liquid–liquid phase separation in organising viral components and the mechanisms by which mutations alter transmissibility and pathogenicity. Continued interdisciplinary efforts are vital for understanding viral emergence, guiding public-health responses and harnessing viruses for gene therapy and vaccine delivery.

Research from Nature Portfolio

Studies have shown that the SARS-CoV-2 nucleocapsid (N) protein undergoes cooperative liquid–liquid phase separation with viral RNA, forming condensates that recruit the polymerase complex and concentrate genome-replication components. Phosphorylation of adjacent serine/arginine-rich regions fine-tunes condensate material properties, linking post-translational modification to the switch between transcriptional and assembly states. High-resolution NMR analyses of the N-terminal domain identified its preference signature for 5′-genomic elements, clarifying how selective RNA binding coexists with genome coating. Complementary single-molecule spectroscopy and all-atom simulations characterised full-length N as a multivalent, dynamic RNA binder whose intrinsically disordered regions adopt transient helices to drive phase separation. Separately, long-read direct RNA sequencing of human adenovirus type 5 transcriptomes uncovered over 11,000 alternatively spliced mRNAs, revealing abundant low-frequency variants that may serve as an evolutionary reservoir and inform the design of attenuated vectors.

Research from all publishers

Outside Nature’s portfolio, parvovirus investigations demonstrated that viral DNA templates induce replication stress by sequestering replication protein A (RPA), shortening host replication forks and triggering ATM-mediated signalling. Restoring RPA rescues fork integrity and boosts viral propagation, pinpointing RPA exhaustion as central to host DNA-damage activation. In another example, the HHV-6B immediate-early protein IE1 binds the NBS1 component of the MRN complex, antagonising ATM activation and impairing homology-directed repair to promote replication and genomic instability. Studies of human airway and nasal organoids compared the replicative fitness of emerging SARS-CoV-2 variants, showing that certain Omicron subvariants exhibit enhanced ACE2-dependent entry and spike-mediated syncytium formation in upper-airway models yet attenuated growth in alveolar systems. Separately, DNA aptamers selected against the SARS-CoV-2 nucleocapsid protein bind with nanomolar affinity across multiple coronaviruses and inhibit replication of prototype and Omicron strains in cell culture, illustrating the potential of nucleic-acid ligands as broad-spectrum antivirals.

Virology publication trend

The graph below shows the total number of articles in virology across all publications each year (not limited to Nature Index journals).

Technical terms

Liquid–liquid phase separation: Demixing of proteins and nucleic acids into membraneless condensates that concentrate specific factors.

Intrinsically disordered region (IDR): A protein segment lacking stable tertiary structure, enabling transient multivalent interactions.

Replication protein A (RPA): A heterotrimeric complex that binds single-stranded DNA to protect and coordinate replication and repair.

ATM kinase: A serine/threonine protein kinase activated by DNA double-strand breaks, orchestrating cell-cycle checkpoints and repair.

Transcriptome: The complete set of RNA transcripts produced by a cell or organism under defined conditions.

References

1. Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates. Nature Communications (2020).
2. The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein. Nature Communications (2021).
3. The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5’-genomic RNA elements. Nature Communications (2023).
4. The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA. Nature Communications (2021).
5. Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution. Communications Biology (2020).
6. Genomes of the autonomous parvovirus minute virus of mice induce replication stress through RPA exhaustion. PLOS Pathogens (2023).
7. The immediate-early protein 1 of human herpesvirus 6B interacts with NBS1 and inhibits ATM signaling. EMBO Reports (2024).
8. Human airway and nasal organoids reveal escalating replicative fitness of SARS-CoV-2 emerging variants. Proceedings of the National Academy of Sciences of the United States of America (2023).
9. Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential anti pan-coronavirus activity. Signal Transduction and Targeted Therapy (2024).