Herpesvirus infections are caused by a family of double-stranded DNA (dsDNA) viruses that establish lifelong infection in humans (1). Eight types of herpesviruses infect humans (see table ). These infections are characterized by alternating lytic (productive) and latent (dormant) phases. Lytic phases may produce symptoms of infection. After initial infection, all herpesviruses enter a latent phase within specific host cells and may subsequently reactivate to the lytic phase. Clinical syndromes due to primary herpesvirus 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. The life cycle and pathogenicity of herpesviruses are shaped by complex persistence and immune system–evasion strategies, making these viruses among the most clinically significant human pathogens.
Despite the fact that the herpesviruses are genetically and structurally similar, they cause a wide array of generally nonoverlapping clinical syndromes.
In contrast to other herpesviruses that are not known to cause 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 |
|---|---|---|
Herpes simplex virus type 1 | Human herpesvirus 1 | Gingivostomatitis, keratoconjunctivitis, tonsillopharyngitis, cutaneous herpes including herpetic whitlow, genital herpes, neonatal herpes, herpes labialis, encephalitis, viral meningitis, esophagitis*, pneumonia*, disseminated infection*, hepatitis*† |
Herpes simplex virus type 2 | Human herpesvirus 2 | Oral and genital herpes, cutaneous herpes including herpetic whitlow, gingivostomatitis, tonsillopharyngitis, herpes simplex keratitis, neonatal herpes, viral meningitis (Mollaret's meningitis), disseminated infection*, hepatitis*† |
Varicella-zoster virus | Human herpesvirus 3 | Varicella (chickenpox), herpes zoster (shingles), disseminated herpes zoster* |
Epstein-Barr virus | Human herpesvirus 4 | Infectious mononucleosis, hepatitis, encephalitis, nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt lymphoma, lymphoproliferative syndromes*, oral hairy leukoplakia*, gastric cancer, multiple sclerosis |
Cytomegalovirus | Human herpesvirus 5 | Cytomegalovirus (CMV) mononucleosis, hepatitis, congenital cytomegalic inclusion disease, hepatitis*, retinitis*, pneumonia*, colitis* |
Human herpesvirus 6A and 6B | — | Roseola infantum, otitis media with fever, encephalitis* |
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 HIV-–related non-Hodgkin lymphomas that grow primarily in the pleural, pericardial, or abdominal cavities as lymphomatous effusions (primary effusion lymphoma) Also linked with some types of multicentric Castleman disease |
* In immunocompromised hosts. | ||
† Uncommonly causes fulminant hepatitis without cutaneous lesions in immunocompromised hosts or pregnant patients. | ||
General reference
1. Dotto-Maurel A, Arzul I, Morga B, Chevignon G. Herpesviruses: overview of systematics, genomic complexity and life cycle. Virol J. 2025;22(1):155. Published 2025 May 22. doi:10.1186/s12985-025-02779-7
Pharmacologic Treatment of Herpesviruses
Medications that have activity against herpesviruses include acyclovir, cidofovir, famciclovir, foscarnet, ganciclovir, idoxuridine (not available in the United States), maribavir, letermovir, penciclovir, trifluridine, valacyclovir, valganciclovir, and vidarabine (see table Medications that have activity against herpesviruses include acyclovir, cidofovir, famciclovir, foscarnet, ganciclovir, idoxuridine (not available in the United States), maribavir, letermovir, penciclovir, trifluridine, valacyclovir, valganciclovir, and vidarabine (see table).
Medications Used to Treat Herpesvirus Infections
Medication | Activity | Uses | Adverse Effects |
|---|---|---|---|
AcyclovirAcyclovir | 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 the renal tubules (primarily with IV use); in patients with renal failure, neurologic toxicity; in patients who are immunocompromised, TTP/HUSRarely, renal toxicity due to precipitation of acyclovir crystals in the renal tubules (primarily with IV use); in patients with renal failure, neurologic toxicity; in patients who are immunocompromised, TTP/HUS |
CidofovirCidofovir | 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 (Fanconi-type syndrome with proteinuria, glucosuria, and bicarbonate wasting) |
Famciclovir (prodrug of penciclovir)Famciclovir (prodrug of penciclovir) | Antiviral spectrum similar to acyclovir (strains resistant to acyclovir also resistant to famciclovir)Antiviral spectrum similar to acyclovir (strains resistant to acyclovir also resistant to famciclovir) | Oral: As effective as acyclovir for oral and As effective as acyclovir for oral andgenital herpes and herpes zoster; more bioavailable than acyclovir after oral administration (which is theoretically important for VZV infection); more bioavailable than acyclovir after oral administration (which is theoretically important for VZV infection) | Infrequent |
FoscarnetFoscarnet | Active against EBV, KSHV, human herpesvirus 6, acyclovir-susceptible and resistant HSV and VZV, and ganciclovir-susceptible and resistant CMVActive against EBV, KSHV, human herpesvirus 6, acyclovir-susceptible and resistant HSV and VZV, and ganciclovir-susceptible and resistant CMV | IV or intravitreal injection: Efficacy similar to that of ganciclovir for treating and delaying progression of Efficacy similar to that of ganciclovir for treating and delaying progression ofCMV retinitis | Renal toxicity in up to one-third of patients if foscarnet is given without adequate hydration, electrolyte imbalances, genital ulcerations (reversible once the medication is stopped)Renal toxicity in up to one-third of patients if foscarnet is given without adequate hydration, electrolyte imbalances, genital ulcerations (reversible once the medication is stopped) |
Ganciclovir Ganciclovir | In vitro activity against all herpesviruses, including CMV, but HSV strains that are resistant to acyclovir are also cross-resistant to ganciclovirIn vitro activity against all herpesviruses, including CMV, but HSV strains that are resistant to acyclovir are 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 (no longer available in the United States) | 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 |
LetermovirLetermovir | Active against CMV | IV or oral: CMV prophylaxis in bone marrow and renal transplant patients | Nausea, vomiting, diarrhea, peripheral edema, cough, headache, fatigue, abdominal pain; drug interactions (eg, increased cyclosporine, tacrolimus, and sirolimus levels, decreased voriconazole levels)Nausea, vomiting, diarrhea, peripheral edema, cough, headache, fatigue, abdominal pain; drug interactions (eg, increased cyclosporine, tacrolimus, and sirolimus levels, decreased voriconazole levels) |
MaribavirMaribavir | Active against CMV | Oral: Used to treat refractory CMV disease | Dysgeusia, diarrhea, nausea, vomiting |
PenciclovirPenciclovir | Active against HSV-1, HSV-2, VZV, and EBV | Topical (cream): Used to treat recurrent herpes labialis in adults | Erythema |
Trifluridine (trifluorothymidine)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)Valacyclovir (prodrug of acyclovir) | Antiviral spectrum similar to that of acyclovirAntiviral spectrum similar to that of acyclovir | Oral: 3–5 times more bioavailable than acyclovir3–5 times more bioavailable than acyclovir | Similar to those of acyclovirSimilar to those of acyclovir TTP/HUS in some patients with advanced HIV and in transplant recipients who receive valacyclovir in higher doses than currently recommended†and in transplant recipients who receive valacyclovir in higher doses than currently recommended† |
Valganciclovir (prodrug of ganciclovir)Valganciclovir (prodrug of ganciclovir) | Similar to ganciclovirSimilar to ganciclovir | Oral: More bioavailable than oral ganciclovirMore bioavailable than oral ganciclovir | Similar to ganciclovirSimilar to ganciclovir |
Vidarabine (adenine arabinoside, ara-A) | 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 1 of the following:
| |||
† Valacyclovir should be used with caution in patients with advanced HIV and in transplant recipients.† 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. | |||
