Herpesviridae
Herpesviridae is a family of viruses encompassing more than a hundred members, of which eight are known to cause infections in humans. These viruses feature a large double-stranded DNA genome encased in an icosahedral capsid, typically ranging from 100 to 300 nanometers in size, and surrounded by a membranous envelope. Most human herpesviruses establish lifelong latency in infected cells, allowing them to reactivate later, which can lead to recurrent symptoms. Commonly known herpesviruses include Herpes Simplex Virus 1 and 2 (HHV-1 and HHV-2), which are associated with oral and genital sores, and Varicella-Zoster Virus (HHV-3), responsible for chickenpox and shingles. Epstein-Barr Virus (HHV-4) can cause infectious mononucleosis and is linked to certain cancers, while Cytomegalovirus (HHV-5) poses a risk during pregnancy. Treatment typically involves antiviral drugs that inhibit viral DNA synthesis, such as acyclovir, which helps manage symptoms but does not eradicate the virus from the body. Herpesviridae infections can affect individuals differently, depending on factors like their immune status and the specific virus involved.
Herpesviridae
- TRANSMISSION ROUTE: Direct contact
Definition
The herpesviridae family comprises more than one hundred viruses. Eight of the viruses are associated with human infections. All known herpesviruses consist of a large double-stranded deoxyribonucleic acid (DNA) genome enclosed within an icosahedral capsid. This capsid ranges in size from 100 to 300 nanometers and is surrounded by a membranous envelope.
Natural Habitat and Features
Most members of the herpesviridae are found naturally in humans. Initial infection generally results in clinical disease that can take different forms depending upon the cells infected. All herpesviruses can undergo latency, in which a virus is retained within a proportion of infected cells but is not undergoing active replication. The virus may be reactivated at any time, resulting in a recurrence of clinical symptoms and the shedding of the virus.
The herpesviruses are largely species-specific. Humans are a primary reservoir for the viruses, though a minimum of one simian virus, H. simiae, also known as monkey B virus and now called cercopithecine herpesvirus-1, can pass from rhesus monkeys to humans.
Pathogenicity and Clinical Significance
The diversity of the human herpesviruses, coupled with the types of cells they infect, result in a variety of diseases with which they are associated. The specific clinical appearance following infection depends upon the site and form of exposure.
Human herpesvirus-1 (HHV-1) and human herpesvirus-2 (HHV-2). HHV-1 and HHV-2, formerly called herpes simplex-1,2, initially infect surface epithelial cells, resulting in cold sores or fever blisters. The virus then establishes latency in nerve ganglia associated with the site of infection. HHV-1 is primarily a childhood infection that leads to sores around the mouth; it is generally transmitted by children who, by touching herpes lesions, pass the virus to others. HHV-2 historically was a sexually transmitted virus that led to genital sores.
Human herpesvirus-1 (HHV-3). Initial exposure to HHV-3, formerly called the varicella-zoster virus, leads to the childhood disease chickenpox. The virus is generally passed through respiratory secretions. As a childhood disease, chickenpox is usually mild; if the first infection is in an adult, however, the disease may be more severe and potentially life-threatening. The virus remains in a latent state within the nerve ganglia. Reactivation of the virus produces a rash, usually in the trunk region, called shingles.
Human herpesvirus-4 (HHV-4). Also called the Epstein-Barr virus, HHV-4 is a respiratory virus infecting the glands of the nasopharynx region. Initial exposure may result in infectious mononucleosis. The virus establishes latency in lymphocytes. The same virus is associated with two forms of cancer: Burkitt’s lymphoma and nasopharyngeal carcinoma, and has been linked to Hodgkin’s disease.
Human herpesvirus-5 (HHV-5). Also known as cytomegalovirus, HHV-5 is passed with respiratory secretions and establishes latency in lymphocytes. The virus is generally harmless in otherwise healthy persons. However, the virus can cross the placenta, so infection in a pregnant woman can lead to severe congenital abnormalities and disorders in the child.
Human herpesvirus-6 (HHV-6) and Human herpesvirus-7 (HHV-7). Associated with roseola in infants, HHV-6 is sometimes referred to as sixth disease, in which children may develop a rash-like illness. It is latent in lymphocytes and is likely passed in respiratory secretions. Also latent in lymphocytes, HHV-7 is not, however, associated with any known disease.
Human herpesvirus-8 (HHV-8). The virus appears harmless in healthy persons, but in immunosuppressed persons, such as those with human immunodeficiency virus infection, the reactivation of HHV-8 may result in Kaposi’s sarcoma.
Drug Susceptibility
All the human herpesviruses establish latency in cells specific to that virus, and all are maintained for the life of the infected person. Antiviral treatment is often useful in suppressing viral growth, limiting the pathological effects of the disease, and reducing the ability of the virus to pass from one person to another. However, the virus is never completely eliminated from the infected person, and recurrence of the infection may sporadically take place.
All the antiviral drugs proven effective in the treatment of Herpesviridae infections have been DNA analogs, molecules that structurally resemble those used in the synthesis of DNA during viral replication but that actually inhibit the process. The principle underlying the use of these drugs takes advantage of the fact that these viruses encode their own unique DNA polymerase, which preferentially incorporates the analogs in place of the correct nucleotides during DNA synthesis. The equivalent cell polymerase, used in replicating cell DNA, is less likely to use these same analogs. Consequently, normal cell replication is unaffected.
The earliest developed of these analogs was acyclovir, a molecule similar in structure to the thymidine normally used in DNA. Incorporation of the drug into replicating DNA inhibits the elongation of the growing strand, blocking viral replication.
Similar analogs, including valacyclovir, vidarabine, and ganciclovir, were developed to treat herpes simplex and other herpesviruses. These analogs act either by directly inhibiting the viral polymerase or blocking the chain growth of replicating DNA.
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