La Crosse virus (LACV) Gc fusion peptide mutants have impaired growth and fusion phenotypes, but remain neurotoxic.
La Crosse virus is a leading cause of pediatric encephalitis in the Midwestern United States and an emerging pathogen in the American South. The LACV glycoprotein Gc plays a critical role in entry as the virus attachment protein. A 22 amino acid hydrophobic region within Gc (1066-1087) was recently identified as the LACV fusion peptide. To further define the role of Gc (1066-1087) in virus entry, fusion, and neuropathogenesis, a panel of recombinant LACV (rLACV) fusion peptide mutant viruses was generated. Replication of mutant rLACVs was significantly reduced. In addition, the fusion peptide mutants demonstrated decreased fusion phenotypes relative to LACV-WT. Interestingly, these viruses maintained their ability to cause neuronal loss in culture, suggesting that the fusion peptide of LACV Gc is a determinant of properties associated with neuroinvasion (growth to high titer in muscle cells and a robust fusion phenotype), but not necessarily of neurovirulence.
Soldan
Samantha S
SS
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA. sssoldan@mail.med.upenn.edu
Hollidge
Bradley S
BS
Wagner
Valentina
V
Weber
Friedemann
F
González-Scarano
Francisco
F
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005347:Fibroblasts / Q000821:virology; D018062:La Crosse virus / Q000235:genetics* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010641:Phenotype; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
D014760:Viral Fusion Proteins