Herpes Simplex Virus Types 1 & 2

• Herpes Simplex 1 and 2 (HSV-1 and HSV-2) are double-stranded linear enveloped DNA viruses.
• Both viruses are associated with erythema multiforme, herpetic whitlow, herpes gladiatorum, and keratoconjunctivitis.
• Asymptomatic shedding is common for both HSV-1 and HSV-2.
• Both viruses belong to the Herpesviridae family and the Alphaherpesvirinae subfamily.
• HSV-2 causes 80 - 90% of genital herpes cases, while HSV-1 causes the remainder.
• HSV-1 is primarily transmitted through saliva, causing infections mainly on the face, and primarily occurs in adults.
• HSV-2 is infection of the genitals, and can spread to the oral cavity.
• Approximately 80% of people in the U.S. are infected with HSV-1, and 40% of those have recurrent cold sores (herpes labialis).
• Most primary HSV-1 infections occur in childhood.
• These viruses replicate in the skin or mucous membranes at the infection site.
• The virus travels up the neuron by retrograde axonal flow and becomes latent in sensory ganglion cells.
• HSV-1 typically becomes latent in the trigeminal ganglia (near the face), while HSV-2 becomes latent in the lumbar and sacral ganglia (near the lower back).
• Reactivation factors include sunlight, hormonal changes, trauma, stress, and fever, leading to recurrent lesions.
• The virus migrates down the neuron and replicates in the skin, causing lesions.

Clinical Symptoms of HSV-1

• Gingivostomatitis: Occurs mainly in children, characterized by fever, irritability, and vesicular lesions in the mouth, lesions heal spontaneously in 2 - 3 weeks, many children are asymptomatic.
• Herpes labialis: Milder, recurrent fever blisters or cold sores that are characterized by crops of vesicles, usually at the mucocutaneous junction of the lips or nose, and recurrences frequently reappear at the same site.
• Encephalitis: Necrotic lesion in one temporal lobe, along with fever, headache, vomiting, seizures, and altered mental status, with a high mortality rate and severe neurological issues in those that survive.
• Eczema herpeticum: Infection of the skin in patients with atopic dermatitis, common in children, with vesicular lesions at the site of the atopic dermatitis.
• Disseminated infections such as esophagitis and pneumonia can occur in immunocompromised patients with depressed T cell function.

Clinical Symptoms of HSV-2

• Many infections are asymptomatic.
• Genital herpes: Painful vesicular lesions on the genitals and anal area, more severe in primary infections than in recurrences and primary infections are associated with fever and inguinal adenopathy.
• Neonatal herpes: Infection in newborns from birth canal contact with vesicular lesions, can range from asymptomatic to severe lesions and encephalitis.
• Aseptic meningitis: Brain and spinal cord infection.

Diagnosis

• The virus can be isolated from lesions by growing it in cell culture.
• Multinucleated giant cells and ground-glass chromatin are typical cytopathic effects.
• A rapid presumptive diagnosis can be achieved through Tzanck smear.
• PCR can detect HSV DNA in spinal fluid for encephalitis diagnosis.
• Serological tests can diagnose primary infections.
• Monoclonal antibodies in ELISA tests can distinguish HSV-1 and HSV-2 by detecting glycoprotein G.

Treatment

• Acyclovir (acycloguanosine and zovirax): Effective for treating encephalitis, systemic diseases, primary and recurrent genital herpes, and neonatal infections.
• Foscarnet: Used for acyclovir-resistant HSV-1.
• Trifluridine: Topical treatment for HSV-1 eye infections.
• Oral Acyclovir: Used for treating HSV infections.
• Valacyclovir (Valtrex) and Famciclovir (Famvir): Used for treating genital herpes.
• HSV-1 and HSV-2 are the only human herpesviruses with substantial nucleotide sequence identity (50% of their genetic material is very similar).