Herpesviridae

Herpesviridae is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein ('to creep'), referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established Herpesvirus as a genus with 23 viruses among four groups. Latent, recurring infections are typical of this group of viruses, though the family name does not refer to latency. Herpesviridae can cause latent or lytic infections. At least five species of the Herpesviridae – HSV-1 and HSV-2 (both of which can cause orolabial herpes and genital herpes), varicella zoster virus (the cause of chickenpox and shingles), Epstein–Barr virus (implicated in several diseases, including mononucleosis and some cancers), and cytomegalovirus – are extremely widespread among humans. More than 90% of adults have been infected with at least one of these, and a latent form of the virus remains in almost all humans. Nine herpesvirus types are known to infect humans: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2, also known as HHV1 and HHV2), varicella-zoster virus (VZV, which may also be called by its ICTV name, HHV-3), Epstein–Barr virus (EBV or HHV-4), human cytomegalovirus (HCMV or HHV-5), human herpesvirus 6A and 6B (HHV-6A and HHV-6B), human herpesvirus 7 (HHV-7), and Kaposi's sarcoma-associated herpesvirus (KSHV, also known as HHV-8). In total, more than 130 herpesviruses are known, some of them from mammals, birds, fish, reptiles, amphibians, and mollusks. All members of the Herpesviridae share a common structure; a relatively large, monopartite, double-stranded, linear DNA genome encoding 100-200 genes encased within an icosahedral protein cage (with T=16 symmetry) called the capsid, which is itself wrapped in a protein layer called the tegument containing both viral proteins and viral mRNAs and a lipid bilayer membrane called the envelope. This whole particle is known as a virion. All herpesviruses are nuclear-replicating—the viral DNA is transcribed to mRNA within the infected cell's nucleus. Infection is initiated when a viral particle contacts a cell with specific types of receptor molecules on the cell surface. Following binding of viral envelope glycoproteins to cell membrane receptors, the virion is internalized and dismantled, allowing viral DNA to migrate to the cell nucleus. Within the nucleus, replication of viral DNA and transcription of viral genes occurs. During symptomatic infection, infected cells transcribe lytic viral genes. In some host cells, a small number of viral genes termed latency-associated transcript (LAT) accumulate, instead. In this fashion, the virus can persist in the cell (and thus the host) indefinitely. While primary infection is often accompanied by a self-limited period of clinical illness, long-term latency is symptom-free. Reactivation of latent viruses has been implicated in a number of diseases (e.g. shingles, pityriasis rosea). Following activation, transcription of viral genes transitions from LAT to multiple lytic genes; these lead to enhanced replication and virus production. Often, lytic activation leads to cell death. Clinically, lytic activation is often accompanied by emergence of nonspecific symptoms, such as low-grade fever, headache, sore throat, malaise, and rash, as well as clinical signs such as swollen or tender lymph nodes and immunological findings such as reduced levels of natural killer cells.