Herpes Simplex Virus (HSV)

Categorization
Genome: DNA Virus, dsDNA Virus Structure: Enveloped Virus, Icosahedral Virus
Overview
  • Herpes Simplex Virus (HSV) is an Alpha-Herpes Virus that is widely distributed throughout the world and establishes latency in neurons.
Transmission
  • HSV can be transmitted through contact with infected saliva or via sexual transmission. Mother-to-child transmission can occur during delivery through an infected birth canal or trans-placentally thus classifying HSV as a TORCHES Organism.
Pathogenesis
  • Typically, primary infection at mucocutaneous surfaces results in florid proliferation of the virus, causing the symptomology and pathology associated with primary mucocutaneous infection (See below). Infection of local somatic or autonomic nerve endings occurs and HSV nucleocapsids undergo axonal reverse transport to the neuronal cell body located within ganglia. Although HSV generally lyses epithelial cells, it enters a state of latency in neurons, characterized by extremely low-level synthesis of a limited set of viral proteins which do not disturb normal neuronal function. This latent state may last for years but the virus can "Reactivate" following certain stressful stimuli including sun exposure, fever, or emotional stress. Upon reactivation, virus is resynthesized by infected neurons, travels down axons, and re-infects the epithelial tissue innervated by the infected neurons. Because the host now has some immunity to the virus, mucocutaneous infections due to reactivations are typically less severe and are shorter in course than the primary infection. Cell-mediated immunity is most imporant for controlling HSV; therefore, immunocompromised patients, especially AIDS patients, can undergo more frequent reactivations as well as potentially serious disseminated disease.
Clinical Consequences
  • Overview
    • HSV can cause a wide range of pathologies depending on the geography of infection as well as the age and immune status of the host. Two highly similar but distinct subtypes of HSV exist, termed HSV-1 and HSV-2, which cause identical clinico-pathological consequences but differ in their propensity to reactivate in particular tissue types. HSV-1 reactivates more frequently in the oral cavity and on the lips whereas HSV-2 tends reactivate more frequently on the genitals.
  • Gingivostomatitis
    • Primary infection is characterized by painful vesicles and ulcers on the oral mucosa, gingiva, as well as lips of the mouth. Primary infections are often accompanied by constitutional symptoms such as fever and occasionally lymphadenopathy. Latency is usually established in the trigeminal ganglion and reactivations are characterized by clusters of vesicles within the oral mucosa or on the border of the lips.
  • Genital Herpes
    • Genital Herpes is characterized by highly painful vesicles or ulcers on the genitals as well as urethritis. In men lesions can be found on the penis and in women lesions can be found on the labia, cervix, vagina, and perineum. Symptoms of urethritis such as dysuria, frequency, and urgency are common. constitutional symptoms are frequent with primary infection as well as lymphadenopathy of the inguinal lymph nodes. Reactivation of the virus generally causes milder symptoms and clusters of vesiculo-ulcerative lesions.
  • Keratitis
    • HSV Infection of the eye can cause keratitis and conjunctivitis. Repeated infection of the cornea can lead to blindness.
  • Encephalitis
    • HSV is a frequent cause of sporadic viral encephalitis and can be quite fatal. HSV Encephalitis manifests with a marked fever and focal Neurological impairments accompanied by a lymphocytic CSF Pleocytosis.
  • Neonatal Herpes
    • Because cell-mediated immunity is weak in neonates, Neonatal HSV infections are fatal nearly half the time. Disease can manifest as extensive mucocutaneous vesiculo-ulcerative lesions, encephalitis, meningitis, or disseminated disease affecting multiple organs.
Treatment
  • Topical or systemic acyclovir is the therapy of choice for most cases of HSV infection. Newer analogs of acyclovir, famciclovir and valacyclovir are also commonly used. In cases where the HSV appears to be Acyclovir-resistant, foscarnet can be used.