Herpes Simplex Virus
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are two strains of the Herpes virus family, Herpesviridae, which cause infections in humans. HSV-1 and 2 are also referred to as Human Herpes Virus 1 and 2 (HHV-1 and HHV-2).
After an initial, or primary, infection, HSV establishes latency, during which the virus is present in the cell bodies of nerves which innervate the area of original outbreak. During reactivation, virus is produced in the cell and transported outwardly via the nerve cell’s axon to the skin. The ability of Herpes virus to establish latency leads to the chronic nature of Herpes infection; after the initial infection subsides, Herpes symptoms may periodically recur in the form of outbreaks of herpetic sores near the site of original infection.
Herpes infections are marked by painful, watery blisters in the skin or mucous membranes (such as the mouth or lips) or on the genitals. The blisters resemble those seen in Chickenpox — an infection caused by a third member of the alpha-Herpesviridae subfamily, Varicella Zoster Virus (VZV), also known as Human Herpes Virus 3 (HHV-3). Lesions heal with a crudescent scab, the hallmark of herpetic disease. Herpes is contagious if the carrier is producing and releasing (“shedding”) virus. This is particularly likely during an outbreak, although individuals may shed virus between outbreaks. Although no cure is yet available, treatments exist which reduce the likelihood of viral shedding. An infection on the lips is commonly known as a “cold sore” or “fever blister”; not to be confused with a canker sore, which is not caused by the HSV virus.
HSV is generally transmitted by direct contact of lips or genitals when the sores are present, or just before they appear (known as shedding). In addition, herpes may be transmitted during childbirth, which can be fatal to the infant. The immature immune system of the child is unable to defend against the virus and even if treated, infection can result in brain damage. Transmission occurs while passing through the birth canal and the risk of infection is minimal if there are no symptoms or exposed blisters during delivery. The first outbreak after exposure to HSV is commonly more severe than future outbreaks, as the body has not had a chance to produce antibodies; this first outbreak also carries the risk of developing meningitis.
Entry and Replication
Entry and replication of the HSV involves interactions of several viral glycoproteins with cell surface receptors or particles. The virus particle contains an envelope which, when bound to specific receptors on the cell surface, will fuse with the cell membrane. This allows entry of the viral particle into the host cell. Initially, glycoprotein C, on the surface of the viral envelope, targets and binds to a cell surface particle, heparan sulfate. This interaction allows for other surface glycoproteins to interact with the host cell. Two major glycoproteins, glycoprotein B and glycoprotein D, also associate with the cell membrane. Glycoprotein D binds specifically to the herpesvirus entry mediator receptor (HVEM), thus providing a strong, fixed attachment to the host cell. Glycoprotein B interacts with host cell surface glycosaminoglycans.
Once bound to the HVEM, glycoprotein D changes its conformation and interacts with glycoproteins H and L, which form a complex. Glycoprotein B interaction with the glycoprotein H and L complex allows the virus to enter into the cell. The viral particle migrates to the nucleus, where the genome is replicated using enzymes from the host cell. Upon entering the cell, an α-TIF protein also joins the viral particle and aids in immediate early Transcription. The virion host shutoff protein (VHF-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. While the viral genome immediately travels to the nucleus, the VHF protein remains in the cytoplasm.
The packaging of the viral particles, which include the genome, core and the capsid, occur in the nucleus. In the nucleus, cleavage of genome concatemers occurs and these are placed into pre-formed capsids. The viral envelope is acquired from the nuclear envelope, more specifically the inner lamellae of the membrane.
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