Abstract and Introduction
Abstract
Human herpesvirus-6 (HHV-6) belongs to the herpesvirus family and is categorized into variant A and B (HHV-6A and HHV-6B). Primary HHV-6 infection in children and its related diseases are almost exclusively caused by HHV-6B and no disease caused by HHV-6A has been identified. The cellular receptor of HHV-6 has been shown to be a human CD46, and its viral ligand is an envelope glycoprotein complex, gH/gL/gQ1/gQ2 in HHV-6A. Furthermore, both cellular and viral lipid rafts play an important role in the HHV-6 entry process, suggesting that HHV-6 may enter its target cells through a lipid raft-associated mechanism.
Introduction
Human herpesvirus (HHV) -6 belongs to the herpesvirus family,[1] which consists of over 200 members divided into α, β and γ subgroups. Only eight herpesviruses commonly infect humans: herpes simplex virus (HSV) type-1 and -2, varicella zoster virus, human cytomegalovirus (HCMV), Epstein–Barr virus, HHV-6 variants A and B, HHV-7 and -8 (Kaposi's sarcoma-associated herpesvirus). The determinants of host species, tissue or cell tropism are thought to work in different steps of the viral lifecycle.
Herpesviruses are enveloped DNA viruses.[2] A typical herpesvirus virion has a dsDNA genome contained inside an icosahedral capsid, and a structural protein layer called the tegument lies between the capsid and the membrane envelope. Latency is a unique infection state of herpesviruses. After the primary infection, herpesviruses can establish latency in their natural host. In this state, virus production ceases, the viral genome assumes a closed circular form, and only a subset of viral proteins is expressed in some herpesviruses. Local stimuli, such as injury, or systemic stimuli, such as physical or emotional stress or hormonal imbalance, can reactivate the latent herpesvirus. Lytic virus replication occurring after reactivation may cause local pathological changes, such as ballooning of cells and the appearance of condensed chromatin within the nuclei of the cells, and eventually lead to disease in the natural host.
Human herpesvirus-6 is a T-cell tropic virus, first isolated from the peripheral blood lymphocytes of patients with lymphoproliferative disorders and AIDS.[3] Clinical isolates of HHV-6 can be categorized into two variants, HHV-6 variant A (HHV-6A) and variant B (HHV-6B), based on their genetic, antigenic and growth characteristics.[4–7] A primary infection by HHV-6 causes acute high fever in children and lasts for approximately 3 days, after which it declines; some patients, especially in Japan, develop a mild skin rash mainly on the trunk, neck and face, which is diagnosed as exanthema subitum.[8–10] HHV-6 infects most infants between 6 and 12 months of age, and can establish a lifelong latency. Thus, more than 90% of the general population is seropositive for this virus.[11] The salivary glands and brain are suspected to be persistent infection sites for HHV-6, and saliva is a vehicle for its transmission, either from mother to child or between children.[12–14] Primary HHV-6 infection and its related diseases in children are almost exclusively caused by HHV-6B, not HHV-6A,[15,16] and no disease caused by HHV-6A has been identified.[17] Following the primary infection, the latency sites for HHV-6 are thought to be monocytes and early bone-marrow progenitor cells.[18,19] HHV-6 reactivation is frequently detected in immunosuppressed patients,[1] such as bone marrow or solid-organ transplant recipients, and HIV patients,[20–24] and viral reactivation in an immunocompromised host has been linked to a variety of diseases, including encephalitis.[25]
Future Microbiol. 2010;5(7):1015-1023. © 2010 Future Medicine Ltd.
Cite this: Human Herpesvirus-6 Entry into Host Cells - Medscape - Jul 01, 2010.
