Herpesvirus (Herpesviridae)

Herpesviruses which affect man are herpes simplex virus type 1 and type 2, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus. The review deals with the more common clinical manifestations of human herpesvirus infections, which occur ubiquitously in all populations throughout the world. Primary infections most commonly occur in childhood. It is a characteristic feature of herpesvirus that they generally remain in a latent form after clearance of the primary infection. The overall majority of clinical problems are related to activated latent infections, viz. recurrent lesions of herpes simplex, herpes zoster with remaining neuralgia in older patients, and in particular herpesvirus infections and reactivation in immunodeficient individuals. Herpes infection during pregnancy may result in severe generalised infection of the newborn. A possible relationship between herpesvirus and cancer, especially between herpesvirus type 2 and cervical cancer and between Epstein-Barr virus and Burkitt's lymphoma are of major interest today.

Herpesviridae is the name of a family of enveloped, double-stranded DNA viruses with similar ultrastructural features. Members of the Herpesviridae family of viruses are classified into the alpha, beta and gamma subfamilies.

Herpesviruses all have icosahedral symmetry and all are about the same size (approximately 200 nm across). They are among the largest viruses.

They replicate in the cell nucleus, have an affinity for cells of ectodermal origin, produce vesicles or pocks, and produce latent infections.

Herpesviruses include eight human viruses (HHV) and numerous animal viruses. The human herpesviruses, are named from 1 to 8.

HHV-1 and HHV-2: Herpes simplex virus, types 1 and 2 ;

HHV-3: Varicella-zoster virus ;

HHV-4: Epstein-Barr virus (EBV) ;

HHV-5: cytomegalovirus

HHV-6 (Roseolovirus) causes "sixth disease" (known as roseola infantum or exanthem subitum).

HHV-7 is closely related to HHV-6 and causes almost the same symptoms.

HHV-8 is a type of rhadinovirus. KSHV- Kaposi's arcoma associated herpes virus causes Kaposi's sarcoma , primary effusion lymphoma and some types of multicentric Castleman's disease.

Varicella-zoster virus causes chickenpox in nonimmune persons and shingles in those who have had chickenpox.

Herpes Simplex Virus 1 and 2 cause “fever-blisters” and genital lesions, respectively.

Cytomegalovirus is the agent of cytomegalic inclusion disease, and Epstein-Barr virus causes infectious mononucleosis.

Each of these viruses may disseminate and kill patients with defective or suppressed immunity.

A principal histologic feature is the formation of Cowdry type A intranuclear inclusions in epithelial and other cells of the host. Those acidophilic (red with eosin) inclusions have a diameter that exceeds half the diameter of the nucleus and are surrounded by a clear zone (“halo”) of vacant nucleoplasm.

Herpes virus infection also cause the formation of syncytial giant cells by aggression and fusion of infected epithelial cells. These giant cells may also contain intranuclear inclusions.

The neurotropic herpes viruses, HSV-1, HSV-2 and VZV, colonize and establish latent infection in human peripheral sensory ganglia. Although all three viruses belong to the same family and establish latent infection in the same tissue, the clinical pattern of their reactivation is quite different.

Latent herpesviruses of humans. Ann Intern Med. 1984 Jun; 100(6):866-80.

The herpesviruses that infect humans characteristically establish a latent infection that may be reactivated later. The consequences of reactivation range from asymptomatic shedding to severe disseminated infection. Varicella-zoster and herpes simplex viruses are both highly neurotropic, establishing nonreplicating infections in sensory ganglia. Latent herpes simplex virus is known to reside in neurons, and the virus-cell interactions involved have been defined to an extent. Cytomegalovirus and Epstein-Barr virus interact with peripheral blood leukocytes. Latent cytomegalovirus infection of human leukocytes has not been proved, although studies in a murine model have implicated B lymphocytes as a repository of latent virus. Epstein-Barr virus is known to persist in a non-replicating state as extrachromosomal DNA in B lymphocytes and to cause "immortalization" of the infected cell; persistence of the viral genome in epithelial cells may also result in malignant transformation, such as nasopharyngeal carcinoma.

Human herpes viruses in pregnancy: cytomegalovirus, Epstein-Barr virus, and varicella zoster virus.Clin Perinatol. 2005 Sep;32(3):671-96.

Herpes simplex virus and varicella-zoster virus: why do these human alphaherpesviruses behave so differently from one another? Rev Med Virol. 2005 Nov-Dec;15(6):393-406.

Human herpes viruses latent infection in the nervous system. Immunol Rev. 1996 Aug;152:157-73

Herpesvirus infection: an overview of the clinical manifestations.Scand J Infect Dis Suppl. 1991;80:15-20