Herpes Stromal Keratitis: Erosion of Ocular Immune Privilege by Herpes Simplex Virus

Jared E Knickelbein; Kristine-Ann Buela; Robert L Hendricks


Future Virology. 2010;5(6):699-708. 

In This Article

HSV Virology

The HSV-1 virion ranges from 180 to 300 nm in diameter.[3] It comprises of an outer-lipid bilayer envelope embedded with glycoproteins, such as glycoprotein (gp)-B, gpC, gpD, gpH and gpL, which facilitate virus attachment, fusion and entry into cells. Beneath the envelope lies the tegument layer, which contains proteins and enzymes important in early virus infection. The innermost layer consists of 162 capsomers that form the nucleocapsid, whose icosahedral shape is shared by all herpes viruses. This capsid contains the large HSV-1 dsDNA genome, consisting of 152,261 base pairs.

The HSV-1 genome is linearly divided into two covalently linked regions, termed unique long (UL) and unique short (US), which are flanked by long and short inverted repeats.[3] HSV-1 has approximately 90 open reading frames, allowing for the transcription of at least 84 unique proteins. Most products of transcription are not spliced, and a few noncoding RNAs are also produced, such as the latency-associated transcript (LAT). Synthesis of viral proteins occurs in a sequential pattern based on the temporal expression of HSV-1 genes in three classes, designated as immediate early (α), early (β) and late (γ). The α genes are the first to be expressed, and their products, such as ICP0, ICP4, ICP22 and ICP27, are the primary regulators of further viral gene expression.[4,5] The expression of the β genes and their protein products, such as viral thymidine kinase and DNA polymerase, depend on the expression of the immediate early proteins. The early proteins function in viral DNA synthesis, and are required for maximum expression of late proteins. Late proteins consist of viral glycoproteins and structural proteins that are likely to be virulence factors. For instance, viruses deficient in the late gene products, gpC, or the virion host shutoff (vhs) protein are defective in causing keratitis.[6–8] Some late proteins can be expressed at very low levels prior to viral DNA synthesis (termed γ1 or leaky late genes, including gpB), while others require viral DNA synthesis for expression (termed γ2 or true late genes, including gpC).

Herpes simplex virus-1 causes several injuries, both structural and biochemical, to the infected cell. Changes, such as modifications in the nucleolus, site-specific chromosomal damage, cytoskeletal and matrix abnormalities, as well as plasma membrane alterations, occur as a result of viral infection.[3] HSV-1 can establish both productive and latent infections, depending on the cell type infected. If the virus enters the lytic phase, replication will ensue in the host cell, causing cell lysis and viral spread to nearby cells. Non-neuronal cells, such as epithelial cells, are specifically vulnerable to this mode of infection. The virus can also infect sensory neurons and travel to neuronal cell bodies via retrograde microtubule-associated transport, where latency is established and persists for the lifetime of the host.


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