Herpes Viruses
Double-stranded DNA, capsid, and tegument encased in a glycoprotein/lipid bilayer envelope.
Alpha Herpes
HSV-1 and HSV-2. Transmitted through direct contact with contaminated saliva or genital fluids. Targets epithelial cells.
Replicates inside the host cell nucleus. Encoded by thymidine kinase and DNA polymerase that are key targets for medication.
Treatment
Only indicated in cases of encephalitis, neonatal infection, or genital disease.
Nucleoside analogs
Inhibit active DNA polymerase of the virus. Toxicity includes renal (crystals in renal tubules), CNS (hallucinations, lethargy), and transaminitis elevation in liver function tests).
Drugs
- Acyclovir: Guanosine (purine) analog phosphorylated by Herpes virus-encoded thymidine kinase to stop DNA Polymerase. Absensce of viral thymidine kinase leads to resistance to Acyclovir.
- Cidofovir: Does not require phosphorylation to become activated and so can be used in cases of acyclovir resistance.
Note: Acyclovir can be used for prophylaxis to decrease risk for partner transmission
Other medications
Non-nucleoside/nucleotide inhibition of DNA polymerase. Toxicity includes CNS, GI, and can cause cytopenias (lower blood cell counts).
Drugs
- Foscarnet: Does not require phosphorylation to become activated and so can be used in cases of acyclovir resistance.
HSV-1
Alpha Herpes.
Skin and mucocutaneous
- Gingivostomatitis: Fever, sore throat, pharyngeal erythema and vesicular lesions of the mouth. Found in children.
- Herpes Labialis (cold sores): Vesicles at mucocutaneous junctions of the lips or nose.
- Herpes whitlow: Lesions of the finger or hand from autoinoculation (e.g., mouth to hand).
- Herpes gladiatorum: Vesicular lesions in the areas of exposure. Found among wrestlers or individuals in close contact.
- Eczema Herpeticum (Kaposi’s varicelliform eruption): Vesicular lesions at sites of atopic dermatitis/eczema.
- Keratoconjunctivitis: Corneal ulcers and conjunctival epithelial lesions.
Visceral
- Disseminated Disease: Esophagitis/pneumonitis. Found in immunocompromised hosts.
- Encephalitis: Fever, headache, vomiting, seizures, altered mental status. Can see necrosis of temporal lobe. Occurs with primary or recurrent infection and has high mortality and neurologic sequelae.
HSV-2
Alpha Herpes.
Genital
Vesicular lesion, can be accompanied by fever and inguinal lymphadenopathy. 60% recurrence rate.
Neonatal
Transmitted via exposure to vesicles in birth canal during delivery
Type 1: Skin, eye, and mouth (see HSV-1 Skin and mucocutaneous)
Type 2: Encephalitis (see HSV-1 Visceral)
Type 3: Disseminated infection (see HSV-1 Visceral)
Varicella Zoster Virus (VZV)
Transmitted via respiratory droplets or direct contact with lesions. Targets epithelial cells.
Primary Varicella: Chicken Pox
Reactivation: Shingles, Zoster
Pathogenesis
Entry via upper respiratory tract and affects sensory neurons which carry them to the flow to the dorsal root ganglia. Latent virus is maintained in the nucleus but does not integrate host DNA. Can reactivate in immunodepressed states.
Clinical features
Painful papulovesicular rash of the extremities/head, fever, malaise, loss of appetite, headache.
Complications
- Pneumonia
- Encephalitis
- Hepatitis (associated with Reye's Syndrome)
- Secondary bacterial skin infections from scratching lesions (e.g., [[Gram Positive Cocci#Group A Streptococcus pyogenes|GAS]])
Post-herpetic neuralgia can also occur, which is severe pain months after the infection.
Treatment
Antiviral therapy with Acyclovir or |Valacyclovir Prevention includes varicella immunoglobulin after exposure especially for at risk individuals. There is also a recombinant, two-dose vaccine available (Shingrix).
Cytomegalovirus (CMV)
Transmitted via transplacental, breast milk, saliva, sexual contact, blood transfusions and organ transplantation. Targets bone marrow and lymphocytes.
Clinical features
- Congenital CMV: Microcephaly, "blueberry muffin" rash, growth retardation, hepatosplenomegaly, seizures, retinitis
- Primary infection: Can cause heterophile-negative mononucleosis (fever, sore throat, fatigue)
- Reactivation: Pneumonitis, esophagitis, colitis hepatitis, retinitis in immunocompromised individuals.
Treatment
For congenital infections and reactivation: Ganciclovir, valganciclovir
For resistance to Ganciclovir: Foscarnet, cidofovir, leflunomide
For transplant recipients: Acyclovir as a prophylaxis
Epstein-Barr Virus (EBV)
Viral capsid antigen. Transmitted via saliva. Targets lymphocytes.
Clinical features
- Infectious mononucleosis: Fever, lymphadenopathy, sore throat, splenomegaly.
- Oral hairy leukoplakia: White lesions or patches on later border of the tongue. Seen in AIDS patients.
Treatment
Not required unless immunocompromised. Decrease immunosuppression in these cases. May consider rituximab (CD20 monoclonal antibody) or valganciclovir.
Human Herpesvirus 6 (HHV-6)
Transmitted via saliva. Targets lymphocytes and monocytes.
Clinical features
- Children: Fever with rash
- Adults: Mononucleosis-type syndrome (fever, adenopathy, encephalitis)
- Reactivation: Meningoencephalitis, myocarditis, pneumonitis, hepatitis, bone marrow failure
Treatment
Antiviral treatment if immunocompromised. Consider Ganciclovir.
Human Herpesvirus 8 (HHV-8)
AKA: Kaposi Sarcoma associated herpesvirus (KSHV). Transmitted via contact with contaminated saliva or genital fluids. Targets vascular endothelial cells.
Affects cell cycle regulation and can lead to cellular proliferation and cancer.
Clinical features
- Children: Fever and maculopapular rash
- Adults: Immunocompromised individuals can present with adenopathy, rash, and GI symptoms
Kaposi Sarcoma
Vascular tumor that develops with impaired CD8 response. It has indolent, cutaneous proliferation in the lower extremities.
Treatment
Direct antiviral therapy: Ganciclovir, cidofovir, foscarnet, adefovirand acyclovir.
May also include chemotherapy for HHV-8 associated malignancies.