Herpesvirus Entry: an Update

Abstract

Members of the Herpesviridae form a large and diverse fam- ily comprised of three subfamilies designated alpha-, beta-, and gammaherpesviruses. Virions are composed of a large DNA genome encased in an icosahedral capsid, which is in turn coated with a layer of proteins called the tegument and an envelope composed of about a dozen viral proteins and glyco- proteins in a lipid bilayer. At least three, sometimes four, of these envelope glycoproteins are absolutely essential for viral entry. The three glycoproteins thought to be essential for the entry of all herpesviruses are designated gB, gH, and gL. The genes for these glycoproteins are conserved, with gB exhibiting the highest degree of sequence similarity. For at least some herpesviruses, gB is a homodimer or homotrimer displayed as a prominent spike. Heterodimerization of gH and gL is a conserved feature, with the addition of another viral protein subunit for some viruses. Common features of herpesvirus biology include a high in- cidence of asymptomatic infections and the establishment of latent infections which can be reactivated to cause recurrent or new episodes of disease. The human herpesviruses exhibit these common features as well as diversity in biology and pathogenesis. They include the alphaherpesviruses, herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and varicella- zoster virus (VZV); the betaherpesviruses, cytomegalovirus (CMV) and human herpesviruses 6 and 7; and the gammaher- pesviruses, Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8). HSV-1 and HSV-2 are responsible for localized mucocutaneous lesions, most commonly, but can also cause meningitis and encephalitis. VZV causes systemic disease with skin lesions during primary infection (chicken pox) and zoster. All three viruses establish latent infections in neurons and can be reactivated from neurons. The betaherpesviruses cause mostly asymptomatic infections in immunocompetent individ- uals and can establish latent infections in several cell types, including leukocytes of various lineages. EBV is the major cause of infectious mononucleosis and is causally associated with various malignancies, including Burkitt's lymphoma, Hodgkin's disease, other lymphomas, and nasopharyngeal car- cinoma. HHV-8 is associated with Kaposi's sarcoma, multicen- tric Castleman's disease, and primary effusion lymphoma.