Overview of Herpesvirus Infections
Eight types of herpesviruses infect humans (see Table: Herpesviruses That Infect Humans). After initial infection, all herpesviruses remain latent within specific host cells and may subsequently reactivate. Clinical syndromes due to primary infection can vary significantly from those caused by reactivation of these viruses. Herpesviruses do not survive long outside a host; thus, transmission usually requires intimate contact. In people with latent infection, the virus can reactivate without causing symptoms; in such cases, asymptomatic shedding occurs and people can transmit infection.
Despite the fact that the herpesviruses are genetically and structurally similar, they cause a wide array of generally non-overlapping clinical syndromes.
In contrast to other herpesviruses which are not associated with malignancy, Epstein-Barr virus (EBV) and human herpesvirus type 8 (HHV-8), also known as Kaposi sarcoma–associated herpesvirus (KSHV), can cause certain cancers.
Roseola infantum is a childhood disease caused by herpesvirus 6 (and sometimes 7).
Herpesviruses That Infect Humans
Common Name |
Other Name |
Typical Manifestations |
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Herpes simplex virus type 1 |
Human herpesvirus 1 |
Gingivostomatitis, keratoconjunctivitis, cutaneous herpes, genital herpes, encephalitis, herpes labialis, viral meningitis, esophagitis*, pneumonia*, disseminated infection*, hepatitis*† |
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Herpes simplex virus type 2 |
Human herpesvirus 2 |
Genital herpes, cutaneous herpes, gingivostomatitis, neonatal herpes, viral meningitis, disseminated infection*, hepatitis*† |
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Varicella-zoster virus |
Human herpesvirus 3 |
Chickenpox, herpes zoster, disseminated herpes zoster* |
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Epstein-Barr virus |
Human herpesvirus 4 |
Infectious mononucleosis, hepatitis, encephalitis, nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt lymphoma, lymphoproliferative syndromes*, oral hairy leukoplakia*, gastric cancer |
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Cytomegalovirus |
Human herpesvirus 5 |
Cytomegalovirus (CMV) mononucleosis, hepatitis, congenital cytomegalic inclusion disease, hepatitis*, retinitis*, pneumonia*, colitis* |
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Human herpesvirus 6 |
— |
Roseola infantum, otitis media with fever, encephalitis* |
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Human herpesvirus 7 |
— |
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Kaposi sarcoma–associated herpesvirus |
Human herpesvirus 8 |
Not a known cause of acute illness but has a causative role in Kaposi sarcoma* and AIDS-related non-Hodgkin lymphomas that grow primarily in the pleural, pericardial, or abdominal cavities as lymphomatous effusions Also linked with multicentric Castleman disease |
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* In immunocompromised hosts. |
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† Uncommonly causes fulminant hepatitis without cutaneous lesions in immunocompromised hosts or pregnant women. |
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Drug Treatment of Herpesviruses
Drugs that have activity against herpesviruses include acyclovir, cidofovir, famciclovir, fomivirsen, foscarnet, ganciclovir, idoxuridine, penciclovir, trifluridine, valacyclovir, valganciclovir, and vidarabine (see Table: Drugs Used to Treat Herpesvirus Infections).
Drugs Used to Treat Herpesvirus Infections
Drug |
Activity |
Uses |
Adverse Effects |
|
Acyclovir |
Active against (in order of potency) HSV type 1 (HSV-1), HSV-2, VZV, and EBV Minimal activity against CMV |
Oral or IV: IV indicated when a higher serum drug level is required, as for herpes simplex encephalitis |
Oral: Infrequent IV: Rarely, renal toxicity due to precipitation of acyclovir crystals; in immunocompromised patients, TTP/HUS |
|
Cidofovir |
In vitro inhibition of a broad spectrum of viruses, including HSV-1, HSV-2, VZV, CMV, EBV, KSHV, adenovirus, HPV, poxviruses, and human polyomavirus (JC and BK viruses) |
IV: Generally used for CMV, but use limited by renal toxicity Intravitreal injection: For CMV retinitis |
Significant renal toxicity |
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Famciclovir (prodrug of penciclovir) |
Antiviral spectrum similar to acyclovir (strains resistant to acyclovir also resistant to famciclovir) |
Oral: As effective as acyclovir for genital herpes and herpes zoster and more bioavailable than acyclovir after oral administration (which is theoretically important for VZV infection) |
Infrequent |
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Fomivirsen |
Potent activity against CMV (antisense oligonucleotide inhibits CMV protein synthesis) |
Intravitreal injection: For patients with HIV infection and CMV retinitis that is resistant to other therapies |
Increased intraocular pressure, corticosteroid-responsive uveitis |
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Foscarnet |
Active against EBV, KSHV, human herpesvirus 6, acyclovir-resistant (and acyclovir-susceptible) HSV and VZV, and ganciclovir-resistant (and ganciclovir-susceptible) CMV Some anti-HIV activity |
IV or intravitreal injection: Efficacy similar to that of ganciclovir for treating and delaying progression of CMV retinitis |
Renal toxicity in up to one third of patients if foscarnet is given without adequate hydration, electrolyte imbalances |
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Ganciclovir |
In vitro activity against all herpesviruses, including CMV, but HSV strains that are resistant to acyclovir also cross-resistant to ganciclovir Typically drug of choice for CMV Used in HIV patients with CMV retinitis |
IV form: Most common Intravitreal injection: For CMV retinitis Oral: Only 6 to 9% bioavailable; requires 12 capsules/day for a standard dose (1 g tid), limiting its usefulness |
Primarily, bone marrow suppression, particularly neutropenia, which sometimes requires treatment* |
|
Idoxuridine |
Active against HSV-1, HSV-2, VZV, vaccinia, and CMV |
Topical: Because of its high systemic toxicity, limited to topical ophthalmic treatment of herpes simplex keratoconjunctivitis |
Irritation, pain, photophobia, pruritus, inflammation or edema of the eyelids Rarely, allergic reactions |
|
Penciclovir |
Active against HSV-1, HSV-2, VZV, and EBV |
Topical (cream): Used to treat recurrent herpes labialis in adults |
Erythema |
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Trifluridine (trifluorothymidine) |
Active against HSV-1 and HSV-2 |
Topical: Ophthalmic treatment of primary keratoconjunctivitis and recurrent keratitis or ulceration caused by HSV-1 and HSV-2 (Systemic use precluded by bone marrow suppression) |
Ocular stinging, palpebral edema Less commonly, punctate keratitis, allergic reactions |
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Valacyclovir (prodrug of acyclovir) |
Antiviral spectrum similar to that of acyclovir |
Oral: 3–5 times more bioavailable than acyclovir |
Similar to those of acyclovir TTP/HUS in some patients with advanced HIV and in transplant recipients who received valacyclovir in higher doses than currently recommended† |
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Valganciclovir (prodrug of ganciclovir) |
Similar to ganciclovir |
Oral: More bioavailable than oral ganciclovir |
Similar to ganciclovir |
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Vidarabine (adenine arabinoside, ara-A) |
For HSV infections |
IV form not used anymore because of neurotoxicity Ophthalmic preparations: Effective for acute keratoconjunctivitis and recurrent superficial keratitis caused by HSV-1 and HSV-2 |
Superficial punctate keratitis with tearing, irritation, pain, and photophobia |
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* Severe neutropenia (< 500 neutrophils/mcL) may require one of the following: |
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† Valacyclovir should be used with caution in patients with advanced HIV and in transplant recipients. |
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CMV =cytomegalovirus; EBV =Epstein-Barr virus; HPV =human papillomavirus; HSV =herpes simplex virus; KSHV =Kaposi sarcoma–associated herpesvirus; TTP/HUS = thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome; VZV =varicella-zoster virus. |
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