Abstract
Herpes simplex viruses (HSVs) cause human oral and genital ulcer diseases. Patients with HSV-2 have a higher risk of acquiring a human immunodeficiency virus infection. HSV-2 is a member of the α-herpesvirinae subfamily that together with the β- and γ-herpesvirinae subfamilies forms the Herpesviridae family. Here, we report the cryo-electron microscopy structure of the HSV-2 C-capsid with capsid-vertex-specific component (CVSC) that was determined at 3.75 A using a block-based reconstruction strategy. We present atomic models of multiple conformers for the capsid proteins (VP5, VP23, VP19C, and VP26) and CVSC. Comparison of the HSV-2 homologs yields information about structural similarities and differences between the three herpesviruses sub-families and we identify α-herpesvirus-specific structural features. The hetero-pentameric CVSC, consisting of a UL17 monomer, a UL25 dimer and a UL36 dimer, is bound tightly by a five-helix bundle that forms extensive networks of subunit contacts with surrounding capsid proteins, which reinforce capsid stability.
Highlights
Herpes simplex viruses (HSVs) cause human oral and genital ulcer diseases
Herpesviruses constitute a large family of dsDNA viruses, which are the causative agents of a range of diseases, including oral and genital blisters, congenital disorders in immunecompromised individuals (Human cytomegalovirus, HCMV) and cancers (Epstein–Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV))[1]
The DNA genome is under considerable pressure within the capsid as shown by cryo-EM micrographs of HSV-1 Ccapsids, where the inter-duplex spacing is measured at ~26 Å, a value comparable to that found in dsDNA bacteriophages and near the theoretical limit for close packing of DNA duplexes[15]
Summary
Herpes simplex viruses (HSVs) cause human oral and genital ulcer diseases. Patients with HSV-2 have a higher risk of acquiring a human immunodeficiency virus infection. 8 Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China These authors contributed : Herpesviruses constitute a large family of dsDNA viruses, which are the causative agents of a range of diseases, including oral and genital blisters (herpes simplex viruses, HSV-1, and HSV-2), congenital disorders in immunecompromised individuals (Human cytomegalovirus, HCMV) and cancers (Epstein–Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV))[1]. Using our recently-developed block-based reconstruction method[24] we have determined the cryo-EM structure of HSV-2 C-capsid at 3.75 Å and have built atomic models for the capsid and CVSC This structural information, together with recently-reported four near-atomic structures spanning all three herpesvirus sub-families, allows us to identify α-herpesvirus-specific structural features, providing insights into the early evolution of herpesviruses
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