Molecular Characterization of Herpesviruses and Host Interactions

Herpesviruses are large enveloped double-stranded DNA viruses that establish lifelong infections in diverse host cells. At the molecular level these pathogens exhibit a multilayered virion architecture, orchestrated by viral scaffold proteins and a rich proteome that mediates entry, replication, latency and reactivation. Entry is initiated by a concerted cascade of envelope glycoproteins engaging cellular receptors to trigger membrane fusion and genome delivery to the nucleus. Post-entry, immediate-early and early viral proteins remodel host transcriptional and chromatin landscapes, subverting innate immune defences and recruiting host enzymes to support viral gene expression. During lytic replication, dynamic assemblies form in nuclear and cytoplasmic compartments to produce progeny virions, while epigenetic regulation at viral genomes underpins the switch between lytic and latent states. Herpesviruses further evade immunity by selectively antagonising or co-opting host factors such as phosphatases, chaperones and signalling adaptors. Recent advances in proteomics, structural biology and functional genomics are illuminating the spatial organisation of viral–host interfaces, with implications for antiviral strategy development and global health.

Research from Nature Portfolio

Recent studies have used crosslinking mass spectrometry combined with quantitative proteomics to derive a spatially resolved interactome map of intact human cytomegalovirus virions, assigning 32 viral proteins to four concentric layers and identifying over 40 host proteins selectively incorporated into specific compartments. In herpes simplex virus type 1 infection, the immediate-early protein ICP22 was shown to impair histone repositioning by interfering with the FACT chaperone, leading to increased chromatin accessibility downstream of genes during transcription termination defects triggered by viral ICP27. Foundational work has also demonstrated that HSV-1 globally disrupts host transcription termination, causing RNA polymerase II read-through beyond polyadenylation sites and reprogramming cellular transcriptomes without inhibiting splicing.

Molecular Characterization of Herpesviruses and Host Interactions publication trend

The graph below shows the total number of articles in molecular characterization of herpesviruses and host interactions across all publications each year (not limited to Nature Index journals).

Technical terms

Virion: A complete, infectious virus particle comprising genomic nucleic acid within a protein capsid and, for enveloped viruses, a lipid membrane bearing viral proteins.

Crosslinking mass spectrometry: A technique using chemical crosslinkers to stabilise protein–protein interactions prior to mass spectrometric analysis, enabling mapping of spatial contacts.

Immediate-early protein: A viral protein expressed immediately upon infection that regulates host transcription and initiates the viral replication programme.

Chromatin accessibility: The degree to which chromatin is open or compact, affecting the ability of transcription factors and polymerases to engage DNA.

Monoclonal antibody: A homogeneous antibody produced by a single B-cell clone, engineered to bind a specific epitope with high affinity.

Glycoprotein gB: A conserved class III fusion protein on herpesvirus envelopes responsible for mediating membrane fusion and viral entry.

References

1. Spatially resolved protein map of intact human cytomegalovirus virions. Nature Microbiology (2023).
2. The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes. Nature Communications (2023).
3. Widespread disruption of host transcription termination in HSV-1 infection. Nature Communications (2015).
4. Development of a highly effective combination monoclonal antibody therapy against Herpes simplex virus. Journal of Biomedical Science (2024).
5. Pathogenesis and virulence of herpes simplex virus. Virulence (2021).
6. Herpes Virus Fusion and Entry: A Story with Many Characters. Viruses (2012).