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Concept Version 10
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Replication of Herpes Simplex Virus

Herpes replication entails three phases: gene transcription, viral assembly in the nucleus, and budding through the nuclear membrane.

Learning Objective

  • Review the herpes simplex viral replication cycle


Key Points

    • Upon entry into the host cell nucleus, three distinct phases of gene transcription and protein synthesis are initiated, producing the immediate-early, early, and late proteins.
    • Viral nucleocapsid assembly occurs within the host cell nucleus.
    • The virus acquires its final envelope by budding into cytoplasmic vesicles.

Term

  • nucleocapsid

    The core structure of a virus, consisting of nucleic acid surrounded by a coat of protein.


Full Text

Following infection of a cell, a cascade of herpes virus proteins, called immediate-early, early, and late, are produced. Research using flow cytometry on another member of the herpes virus family, Kaposi's sarcoma-associated herpesvirus, indicates the possibility of an additional lytic stage, delayed-late. These stages of lytic infection, particularly late lytic, are distinct from the latency stage. In the case of HSV-1, no protein products are detected during latency, whereas they are detected during the lytic cycle.

Herpes simplex virus

Structure of the conserved core of the herpes simplex virus transcriptional regulatory protein VP16.

The early proteins transcribed are used in the regulation of genetic replication of the virus. On entering the cell, an α-TIF protein joins the viral particle and aids in immediate-early transcription. The virion host shutoff protein (VHS or UL41) is very important to viral replication. This enzyme shuts off protein synthesis in the host, degrades host mRNA, helps in viral replication, and regulates gene expression of viral proteins. The viral genome immediately travels to the nucleus but the VHS protein remains in the cytoplasm.

HSV replication

Entry of HSV into the host cell involves interactions of several glycoproteins on the surface of the enveloped virus, with receptors on the surface of the host cell. The envelope covering the virus particle, when bound to specific receptors on the cell surface, will fuse with the host cell membrane and create an opening, or pore, through which the virus enters the host cell. An enzyme shuts off protein synthesis in the host, degrades host mRNA, helps in viral replication, and regulates gene expression of viral proteins.

The late proteins form the capsid and the receptors on the surface of the virus. Packaging of the viral particles — including the genome, core and the capsid - occurs in the nucleus of the cell. Here, concatemers of the viral genome are separated by cleavage and are placed into pre-formed nucleocapsids. HSV-1 undergoes a process of primary and secondary envelopment. The primary envelope is acquired by budding into the inner nuclear membrane of the cell. This then fuses with the outer nuclear membrane releasing a naked capsid into the cytoplasm. The virus acquires its final envelope by budding into cytoplasmic vesicles.

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