Herpesviridae

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Properties of Herpesviridae 318

Herpes Simplex Viruses 323

Varicella-Zoster Virus .330

Cytomegalovirus 334

Human Herpesvirus 6 341

Epstein-Barr Virus 343

Herpes B Virus 346

Further Reading 346

All herpesviruses have the capacity to persist in their hosts indefinitely in the form of an episome in the nucleus of the cells that harbor them. Virtually every vertebrate species that has been carefully searched is found to support at least one host-specific herpesvirus which has evolved with that host species for millennia. Sometimes, as in humans, host-specific herpesviruses of different subfamilies occupy distinct ecologic niches, noncompetitively, in particular types of cells within a given individual (Table 20-1). Varicella (chick-enpox) and herpes simplex viruses establish latent infections in neurons. On reactivation, the varicella virus precipitates an attack of herpes zoster (shingles), whereas herpes simplex type 1 typically causes recurrent attacks of labial herpes; herpes simplex type 2 is mainly responsible for genital herpes. Cytomegalovirus, Epstein-Barr (EB) virus, and human herpesvirus 6 (HHV-6) persist in lymphocytes. With the control of rubella by immunization, cytomegalovirus is now the major infectious cause of mental retardation and other congenital defects. EB virus is the etiologic agent of infectious mononucleosis and is associated with two types of human cancer, a carcinoma and a lymphoma. HHV-6 causes a common exanthem in children.

The importance of these six human pathogens is increasing as a result of developments in modern medicine and changing sexual practices. Herpesviruses are frequently reactivated in AIDS and following immunosuppressive therapy for organ transplantation or cancer. Under these circumstances, or in infections of the fetus or newborn infant, lethal disseminated disease may occur. Although most herpesviruses pose unsolved problems for vaccine development, some of them are amenable to antiviral chemotherapy.

Table 20-1

Herpesviruses of Humans

Subfamily/genus

Official name

Vcrnactilar name

Biological properties

Alphiihi'tpcii'nvttie Swipltwwiu*

Vatui'Voi'ini*

Pclnhn ¡'t'St'iriiinc

CytiWH'nitUwirns

Rtrvolnviriis

GamitinheiptwrniMC l,i/inphocri/ptovirti^

Human herpesvirus I Human herpesvirus 2 Ce ret >pitliecine herpesvirus 1 Human herpesvirus 3

Human herpesvirus 5

Human herpesvirus 6

I ierpes simplex virus 1 Herpes simplex virus 2 Simian herpes B virus

Vancella-v.oster virus

Cytomegalovirus

Human herpesvirus 4 Epstein-Barr (EB) virus

Fast-growing, cytolytic Latent in neurons

Slow-growing, cytomegalic Latent in salivary glands, kidneys Latent in macrophages, lymphocytes

Lymphoproliferative Latent in B lymphocytes

Properties of Herpesviridae

The herpesvirus virion comprises four concentric layers: an inner core, surrounded by an icosahedral capsid, then an amorphous tegument, and finally an envelope (Table 20-2). The DNA genome is wound like a ball of wool and is associated with a protein core with the shape of a torus or doughnut which appears to be suspended by fibrils anchored to the inner side of the surrounding capsid. The capsid is an icosahedron, 100 nm in diameter, composed of 162 hollow capsomers 150 hexarners and 12 pentamers (Fig. 20-1B). Surrounding the capsid is a layer of globular material, known as the tegument, which is enclosed by a typical lipoprotein envelope with numerous small glycoprotein peplomers (Fig. 20-1 A). The envelope is fragile and the virion somewhat pleomorphic, ranging in diameter from 120 to 200 nm.

Table 20-2

Propeities of Herpesviruses

Sphencal enveloped virions, 120-200 nm (usually about 150 nm) in diameter Icosahedral capsul, 100-110 nm, with 162 capsomers; surrounded by amorphous tegument, then lipid envelope containing numerous different glycoproteins, some forming peplomers Linear dsDNA genome with reiterated sequences characteristic of the genus, 125-229 kbp, associated with toroid protein core Replu ales in nucleus, with sequential transcription and translation of immediate early («), early (P), and late (y) genes producing <*, p, and y proteins, respectively, the earlier (if which legulate transcription from later genes DNA replication and encapsidation incur in nucleus, envelope is acquired by budding through nuclear membrane Productive infection in permissive cells is cytocidal, intranuclear inclusions, sometimes cytomegalic cells m syncytia Establish latent infections, with genome persisting m Ihe nucleus of neurons or lymphocytes, only a small subset of genes is expressed; reactivation triggers replication and recurrent or continuous shedding of infectious virus

t m dftk W

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