Date Published: July 27, 2011
Publisher: Hindawi Publishing Corporation
Author(s): Melissa Batonick, Gail W. Wertz.
Human respiratory syncytial virus (HRSV) is an enveloped RNA virus that assembles and buds from the plasma membrane of infected cells. The ribonucleoprotein complex (RNP) must associate with the viral matrix protein and glycoproteins to form newly infectious particles prior to budding. The viral proteins involved in HRSV assembly and egress are mostly unexplored. We investigated whether the glycoproteins of HRSV were involved in the late stages of viral replication by utilizing recombinant viruses where each individual glycoprotein gene was deleted and replaced with a reporter gene to maintain wild-type levels of gene expression. These engineered viruses allowed us to study the roles of the glycoproteins in assembly and budding in the context of infectious virus. Microscopy data showed that the F glycoprotein was involved in the localization of the glycoproteins with the other viral proteins at the plasma membrane. Biochemical analyses showed that deletion of the F and G proteins affected incorporation of the other viral proteins into budded virions. However, efficient viral release was unaffected by the deletion of any of the glycoproteins individually or in concert. These studies attribute a novel role to the F and G proteins in viral protein localization and assembly.
Human respiratory syncytial virus (HRSV) is the leading viral cause of serious pediatric respiratory tract disease worldwide and a common cause of morbidity in the elderly [1, 2]. Currently there is no vaccine available and the only treatment is a monoclonal antibody given to high-risk infants . Research into vaccine development and therapeutic design is ongoing but an obvious hurdle is the lack of a complete understanding of the replication cycle. The role of the individual viral gene products in each step of virus replication, particularly in the assembly and release of viral particles, is unclear.
The major HRSV structural proteins are the nucleocapsid protein (N), the matrix (M) protein, and the F, G, and SH glycoproteins, all of which associate at the plasma membrane for viral assembly and release. Little is known about the protein requirements of HRSV during the late stage of virus replication. It has been established for many paramyxoviruses that the M protein is necessary for the formation of viral particles [19–25], but the involvement of the glycoproteins varies depending upon the virus. The HRSV glycoproteins have defined roles in attachment and entry, but delineating their potential roles in the downstream steps of the replication cycle is difficult due to the necessity of the F protein for viral entry into cells.