Respiratory Syncytial Virus Attachment Glycoprotein Contribution to Infection Depends on the Specific Fusion Protein

• Type of Material: Article
• Authors: Jia Meng, Emory University; Anne L. Hotard, Emory University; Michael G. Currier, Emory University; Sujin Lee, Emory University; Christopher C. Stobart, Emory University; Martin Moore, Emory University
• Language: English
• Date: 2016-01-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2015, American Society for Microbiology.
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.02140-15
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 90
• Issue: 1
• Start Page: 245
• End Page: 253
• Grant/Funding Information: This study was also supported by funds from Emory University and CHOA.; National Institute of Allergy and Infectious Diseases (NIAID) provided funding to Michael M. Moore under grant numbers 1R01AI087798 and 1U19AI095227.; Additional support was provided by the NIH through Emory Vaccinology Training Grant T32AI074492 (Christopher C. Stobart), by Emory and CHOA under joint grant number 33515 (Michael G. Currier, Christopher C. Stobart, Sujin Lee, and Martin L. Moore), and by Emory through Nelson Memorial Fund R6336510 (Anne L. Hotard and Martin L. Moore).; HHS; NIH
• Keywords: Virology; IDENTIFICATION; INHIBITOR; HUMAN METAPNEUMOVIRUS FUSION; ENTRY; GLYCOSAMINOGLYCANS; Life Sciences & Biomedicine; REPLICATION IN-VITRO; LACKING; HEPARIN; Science & Technology; BALB/C MICE; SH
• Research Categories: Biology, Virology; Health Sciences, General

Abstract

Human respiratory syncytial virus (RSV) is an important pathogen causing acute lower respiratory tract disease in children. The RSV attachment glycoprotein (G) is not required for infection, as G-null RSV replicates efficiently in several cell lines. Our laboratory previously reported that the viral fusion (F) protein is a determinant of strain-dependent pathogenesis. Here, we hypothesized that virus dependence on G is determined by the strain specificity of F. We generated recombinant viruses expressing G and F, or null for G, from the laboratory A2 strain (Katushka RSV-A2GA2F [kRSV-A2GA2F] and kRSV-GstopA2F) or the clinical isolate A2001/2-20 (kRSV-2-20G2-20F and kRSV-Gstop2-20F). We quantified the virus cell binding, entry kinetics, infectivity, and growth kinetics of these four recombinant viruses in vitro. RSV expressing the 2-20 G protein exhibited the greatest binding activity. Compared to the parental viruses expressing G and F, removal of 2-20 G had more deleterious effects on binding, entry, infectivity, and growth than removal of A2 G. Overall, RSV expressing 2-20 F had a high dependence on G for binding, entry, and infection.