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

• 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
• Journal Title: Journal of Virology
• Volume: Volume 90, Number 1
• Publisher: American Society for Microbiology | 2016-01-01, Pages 245-253
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1128/JVI.02140-15
• Subjects: Biology, Virology; Health Sciences, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Virology; HUMAN METAPNEUMOVIRUS FUSION; REPLICATION IN-VITRO; BALB/C MICE; IDENTIFICATION; ENTRY; INHIBITOR; HEPARIN; LACKING; SH; GLYCOSAMINOGLYCANS

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.