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Herpesviruses (excluding Epstein–Barr virus) 

Herpesviruses (excluding Epstein–Barr virus)

Herpesviruses (excluding Epstein–Barr virus)

J.G.P. Sissons



Herpes simplex virus encephalitis—rare mutations of Toll-like Receptor 3 signalling pathway associated with primary HSV encephalitis in children.

Human cytomegalovirus disease (HCMVD)—in the face of ganciclovir resistance other drugs are being tested including artesunate.

HCMV vaccine—a recombinant glycoprotein B based HCMV vaccine in seronegative women reduced incidence of maternal and congenital CMV infection.

Kaposi sarcoma—pathogenesis of angioproliferative and inflammatory Kaposi’s sarcoma lesions, ‘paracrine neoplasia’.

Updated on 31 May 2012. The previous version of this content can be found here.
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date: 28 April 2017

Eight human herpesviruses, all with a linear double-stranded DNA genome and divided into alpha-, beta-, and gamma-subfamilies on the basis of genomic and biological properties, share the capacity to produce latent infection. The diseases they cause may result from primary infection, or reactivation of the virus from latency, and tend to be more severe in immunosuppressed patients. Diagnosis of the various herpesvirus infections may be made on clinical grounds alone, by culture or demonstration of viral particles by electron microscopy of relevant samples, by serological testing, or (increasingly) by PCR-based tests.

Herpes simplex viruses (HSV)

These two alpha-herpesviruses infect epithelial cells and become latent in the central nervous system. (1) HSV-1—transmitted by direct contact with infected secretions from a carrier; predominantly causes orofacial infections; becomes latent in the trigeminal ganglion; reactivation may give rise to recurrent orolabial mucosal ulcers (‘cold sores’) on the lips or skin around the mouth; is the commonest identified cause of acute sporadic encephalitis occurring in immunocompetent subjects in Western countries. (2) HSV-2—usually acquired through sexual contact and is the predominant cause of genital HSV infection, which may also be recurrent.

Treatment of both HSV-1 and HSV-2 is with aciclovir, which is preferentially phosphorylated in HSV-infected cells, or other newer related drugs (famciclovir and valaciclovir). Oral treatment is used in immunocompetent patients, but intravenous therapy is indicated in severe infections, encephalitis and in immunosuppressed patients.

Varicella zoster virus (VZV)

This alpha-herpesvirus is presumed to spread by the respiratory route and after an incubation period of 10 to 20 days causes varicella (chickenpox), predominantly an exanthematous disease of childhood, but which may be complicated in adults by pneumonitis and encephalitis. The virus becomes latent in dorsal root ganglia after primary infection, whence it can reactivate to cause herpes zoster (shingles), with pain, erythema, and vesicular lesions occurring in a dermatomal distribution, particularly in elderly and immunosuppressed individuals. Treatment of severe varicella or herpes zoster is with aciclovir, with higher doses being required than for HSV. A live attenuated VZV vaccine is available: this induces 90% protection from natural varicella in children, and also diminishes the incidence of zoster and postherpetic neuralgia when given to older age groups.

Human cytomegalovirus (HCMV)

This beta-herpesvirus is the largest human herpesvirus. Infection is spread by close contact with body fluids of infected individuals: from 50 to 100% of adults are seropositive, depending on socioeconomic and sexual risk, with myeloid lineage cells being a principal site of HCMV latency. Primary infection in children and adults is usually asymptomatic, but infectious mononucleosis clinically indistinguishable from that caused by primary Epstein–Barr virus (EBV) infection can be produced (see Chapter 7.5.3), and HCMV can produce severe disease in two particular situations. (1) Fetal infection—congenital HCMV infection occurs in around 0.5 to 1% of live births in developed countries; most infected babies are asymptomatic, but classical ‘cytomegalic inclusion disease’ has a high mortality and surviving infants have mental, visual, and hearing impairment. (2) Infection in patients who are immunosuppressed patients—the most serious forms are pneumonitis in bone marrow transplant recipients and retinitis in HIV/AIDS patients. Specific treatment for HCMV is usually with ganciclovir, which requires intravenous administration and has limiting side effects including myelotoxicity; valganciclovir has higher oral bioavailability and is particularly used for prophylaxis.

Human herpesvirus 6 and 7 (HHV-6 and 7)

These are beta-herpesviruses, most probably transmitted via maternal saliva. Primary infection with HHV-6 in young children is associated with roseola infantum (exanthem subitum, sixth disease), and also with a febrile illness without rash. More than 90% of children are seropositive for HHV-6 by 2 years of age. HHV-6 reactivation may occur in immunosuppressed solid-organ and bone marrow transplant recipients, but it is not clear that HHV-6 causes disease in these patients. HHV-6 sensitivity to antiviral drugs corresponds with that of HCMV, but no treatment is usually required. HHV-7 has been associated with some cases of roseola, but there is no other evidence for its being pathogenic.

Human herpesvirus-8 (HHV-8)

This member of the rhadinovirus (gamma 2-herpesvirus) family is the most recently discovered human herpesviruses, having been isolated from Kaposi’s sarcoma tissue in 1994. The mechanism of transmission is probably by saliva and sexual contact; reported seroprevalence is around 50% or more in many African adult populations, but 5% or less in blood donors in the United Kingdom and the United States of America, with intermediate rates in Italy and other Mediterranean countries.

HHV-8 (as other gamma-herpesviruses such as EBV) is potentially oncogenic: it is clearly associated with (1) Kaposi’s sarcoma—HHV-8 can be detected by PCR in the blood of nearly all cases. Manifests clinically as purplish brown macules, papules and plaques, and is described in four clinical settings: (a) the classic form—typically presents in elderly Mediterranean or Jewish men with lesions on the extremities and an indolent course; (b) the endemic African form—accounts for 10% of cancer in equatorial Africa and is similar clinically to the classic form of the disease; (c) in patients with immunodeficiency states such as transplant recipients—lesions are more widespread and rapidly progressive, but visceral involvement is unusual; and (d) the AIDS-associated form—with widespread cutaneous lesions, involvement of the oral mucosa, visceral lesions in the lungs or gastrointestinal tract, and sometimes rapid progression. Kaposi’s sarcoma lesions may regress with antiretroviral treatment, withdrawal of immunosuppression, and the disease can also be treated with radiation therapy and (for widespread cutaneous or visceral disease) with chemotherapy. (2) Primary effusion lymphoma—HHV-8 is present in the tumour cells of all cases of this rare and aggressive type of B cell lymphoma that presents in patients with AIDS. (3) Multicentric Castleman’s disease (angiofollicular lymph node hyperplasia)—HHV-8 is present in most cases of this condition, especially those associated with HIV.

Cercopithecine herpesvirus 1

This alpha-herpesvirus (formerly named herpes B virus) is closely related to HSV, and found in Old World monkeys, its natural host. Transmission to humans from monkey bites results in a high incidence of severe disease, with progressive encephalitis. Treatment is with aciclovir or ganciclovir, but morbidity and mortality are high.

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