Structural Research of Herpesviridae

The Herpesviridae are a group of double-stranded DNA viruses that replicate in the nuclei of a wide range of vertebrates and accomplish infection of host cells by fusion of the viral membrane with the plasma membrane or the membrane of endocytosed vesicles. The family is divided into three subfamilies with 17 genera, nine of which are human herpesviruses (HHV), and herpes simplex virus type 1 (HSV-1) is one of the most widely spread pathogens in humans. Members of Herpesviridae are endemic worldwide and cause a variety of diseases, including herpes labialis, genital herpes, stromal keratitis, meningitis, and encephalitis. In recent years, to explore herpesvirus infection therapies, researchers intend to address this issue through structural information on drug targets.

    Figure 1. The overall structure of HSV-1. (Dai X, Zhou ZH., 2018)

The Unique Four-Layer Structure of Herpesviruses

• Core: Herpesviruses are large double-stranded DNA viruses with a core consisting of a single linear dsDNA molecule and a genome length of 240 kbp.
• Capsid: Surrounding the core is a complex T = 16 icosahedral capsid with a diameter of 1,250 Å, containing 162 capsids arranged in 150 hexagons, 11 penta-neighborhoods, and an entrance.
• Ectoderm: The ectoderm consists of an inner layer and an outer layer, between the capsid and the envelope, and is amorphous. It consists of viral enzymes.
• Envelope: The envelope is the outer layer of the viral particle and consists of viral glycoproteins, forming a network of spikes, essential for viral entry and viral morphogenesis.

Progress in Structural Research on the Herpesviridae

HSV-1 is a typical member of the Herpesviridae family and belongs to the subfamily of α-herpesviruses.HSV-1 establishes latency in neurons and can replicate in the brain. The researchers performed three-dimensional image reconstruction by cryo-electron microscopy to reveal the structure of the capsid of HSV-1 with the unique portal apex of the infectious viral particle at 3.5 Å resolution. The research results provide new insights into the understanding of the herpesvirus capsid and virion assembly and inform the search for new antiviral targets.

Figure 2. Structure of the HSV-1 capsid and ectodermal proteins. (Dai X, Zhou ZH., 2018)

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References

1. Dai X, Zhou ZH. Structure of the herpes simplex virus 1 capsid with associated tegument protein complexes. Science. 2018. 360(6384): eaao7298.
2. McElwee M, et al. Structure of the herpes simplex virus portal-vertex. PLoS Biol. 2018. 16(6): e2006191.
3. Gatherer D, et al. ICTV Virus Taxonomy Profile: Herpesviridae 2021. J Gen Virol. 2021. 102(10): 001673.