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Overview of Herpesvirus Infections

By

Kenneth M. Kaye

, MD, Brigham and Women’s Hospital, Harvard Medical School

Last full review/revision Oct 2019| Content last modified Oct 2019
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Topic Resources

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).

Table
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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*, disseminated infection*, 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

Cytomegalovirus

Human herpesvirus 5

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

Human herpesvirus 6

Human herpesvirus 7

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 immunocompromised hosts or pregnant women.

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).

Table
icon

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

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

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

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

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

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: 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/mcL) 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.

Drugs Mentioned In This Article

Drug Name Select Trade
VALCYTE
VIROPTIC
VALTREX
FAMVIR
CYTOVENE
DENAVIR
VISTIDE
FOSCAVIR
ZOVIRAX
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