Integrins are represented by the circles linked with a line
Integrins are represented by the circles linked with a line. to its extracellular domain name was tested in the fusion assay, confirming that this domain name was important for VZV fusion. In addition, reduced spread was observed in V knockdown Vatiquinone cells infected with the VZV pOka strain relative to that of the control cells. This was exhibited by reductions in plaque size, replication kinetics, and virion entry in the V subunit knockdown cells. Thus, the V integrin subunit is usually important for VZV gB/gH-gL fusion and contamination. IMPORTANCE Varicella-zoster computer virus (VZV) is a highly infectious pathogen that causes chickenpox and shingles. A common complication of shingles is the excruciating condition called postherpetic neuralgia, which Vatiquinone has proven difficult to treat. While a vaccine is now available, it is not recommended for immunocompromised individuals and its efficacy decreases with the recipient’s age. These limitations spotlight the need for new therapies. This study examines the role of integrins in membrane fusion mediated by VZV glycoproteins gB and gH-gL, a required process for VZV Vatiquinone contamination. This knowledge will further the understanding of VZV entry and provide insight into the development of better therapies. INTRODUCTION Varicella-zoster computer virus (VZV) is an alphaherpesvirus and a host-specific Rabbit polyclonal to ATF2 human pathogen that causes the diseases varicella and herpes zoster, commonly known as chickenpox and shingles (1). Prior to the approval of attenuated vaccines by the Food and Drug Administration, varicella was endemic in the United States population and it was estimated that one in three individuals would develop zoster in their lifetime (1, 2). The program for universal varicella vaccination of children in the United States has proven to be successful in preventing disease by reducing varicella incidence by 57% to 90% (3). The zoster vaccine has been effective in reducing the zoster incidence by 51.3% (4). Individuals afflicted with zoster risk developing postherpetic neuralgia (PHN), a debilitating, painful condition that can Vatiquinone last weeks to months after the acute herpes zoster rash has healed (1). Effective therapies are not currently available to treat PHN, as the cause of pain associated with this condition has not been clarified. While the vaccine can significantly reduce the incidence of herpes zoster and PHN, its effectiveness has been reported to wane over time (5). Critically, the attenuated VZV vaccines Vatiquinone are contraindicated for immunocompromised individuals. These limitations spotlight the importance of identifying new targets for drug and vaccine development that focus on essential steps in VZV infection. Herpesvirus membrane fusion is an essential first step of virion entry that allows the nucleocapsid to gain access to the cytoplasm of the host cell (6). The formation of the multinucleated cells called syncytia is a consequence of membrane fusion and is associated with VZV-induced pathology in infected skin and neuronal tissue (7, 8). Fusion is induced by a conserved complex of herpesvirus glycoproteins consisting of gB and the heterodimer gH-gL, which are present on the virion and expressed on the surface of infected cells (9). Expression of VZV gB and gH-gL is necessary and sufficient to induce fusion, in contrast to other herpesviruses which require additional virally encoded accessory proteins, such as gD for herpes simplex virus (HSV), gp42 for Epstein-Barr virus (EBV) for certain cell types, and gO or UL128/UL130/UL131 for human cytomegalovirus (HCMV) (9,C13). Efforts to identify cellular components that contribute to VZV gB/gH-gL-mediated fusion activity have been hampered by the highly cell-associated nature of VZV in cell culture. This has made it challenging to study the stages of VZV infection, including fusion, because of the difficulty in generating a purified cell-free virus inoculum with a high titer, which is in contrast to HSV, which releases complete virions into the culture media (14,C16). Three cell proteins, cation-independent mannose 6-phosphate receptor (MPRci), insulin-degrading enzyme (IDE), and myelin-associated glycoprotein (MAG), have been proposed to function as receptors for VZV entry. MPRci, which binds mannose 6-phosphate groups, is required for cell-free VZV infection of MeWo cells (17). However, MPRci is unlikely to be directly involved in fusion because.