Mechanism of altered Sindbis virus neurovirulence associated with a single-amino-acid change in the E2 Glycoprotein.
The mechanism by which amino acid changes in the E1 and E2 surface glycoproteins of Sindbis virus affect neurovirulence is unknown. We have studied two recombinant viruses which differ in virulence. One (TE) contains Gly and the other (TES) contains Arg at position 172 in E2. TE causes more rapid death than TES in newborn mice. Both viruses replicate similarly in nonneuronal cells, but TE replicates more rapidly in the brains of newborn mice and in neuroblastoma cells. TE also induces earlier viral RNA synthesis in neuroblastoma cells. 35S-labeled TE binds more efficiently to brain and neuroblastoma cells, but not to nonneuronal cells, than TES. We propose that a region of the E2 glycoprotein affected by the amino acid occupying position 172 is important for binding to an alphavirus receptor on neurons and influences neurovirulence by this mechanism.
Tucker
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Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Griffin
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D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000382:microbiology; D002460:Cell Line; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000382:microbiology; D012845:Sindbis Virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
D014759:Viral Envelope Proteins; C064950:glycoprotein E2, Sindbis virus