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Overview of Herpesvirus Infections

By Kenneth M. Kaye, MD, Associate Professor, Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School

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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. 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.

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

Herpes simplex virus type 1

Human herpesvirus 1

Gingivostomatitis, keratoconjunctivitis, cutaneous herpes, genital herpes, encephalitis, herpes labialis, viral meningitis, esophagitis*, pneumonia*, hepatitis*,†

Herpes simplex virus type 2

Human herpesvirus 2

Genital herpes, cutaneous herpes, gingivostomatitis, neonatal herpes, viral meningitis, disseminated infection*, hepatitis*,†

Varicella-zoster virus

Human herpesvirus 3

Chickenpox, herpes zoster, disseminated herpes zoster*

Epstein-Barr virus

Human herpesvirus 4

Infectious mononucleosis, hepatitis, encephalitis, nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt lymphoma, lymphoproliferative syndromes*, oral hairy leukoplakia*


Human herpesvirus 5

CMV mononucleosis, hepatitis, congenital cytomegalic inclusion disease, hepatitis*, retinitis*, pneumonia*, colitis*

Human herpesvirus 6

Roseola infantum, otitis media with fever; encephalitis

Human herpesvirus 7

Roseola infantum

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

*In immunocompromised hosts.

Uncommonly causes fulminant hepatitis without cutaneous lesions in immunocompetent hosts.

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




Adverse Effects


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


In vitro inhibition of a broad spectrum of viruses, including HSV-1, HSV-2, VZV, CMV, EBV, KSHV, adenovirus, HPV, and human polyomavirus (JC and BK viruses)

IV: Generally used for CMV, but use limited by renal toxicity

Significant renal toxicity

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)



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


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: 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


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 patients with both HIV and CMV retinitis

IV form: Most common

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*


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


Active against HSV-1, HSV-2, VZV, CMV, and EBV

Topical (cream): Used to treat recurrent herpes labialis in adults


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

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

Valganciclovir (prodrug of ganciclovir)

Similar to ganciclovir

Oral: Taken as two 450-mg tablets once/day or q 12 h (more bioavailable than oral ganciclovir)

Similar to ganciclovir

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

*Severe neutropenia (< 500 neutrophils/μL) may require one of the following:

  • Bone marrow stimulation with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor

  • Discontinuation of ganciclovir

  • Reduction of the dose

Valacyclovir should be used with caution in patients with advanced HIV and in transplant recipients.

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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