The respiratory syncytial virus subgroup B attachment glycoprotein: analysis of sequence, expression from a recombinant vector, and evaluation as an immunogen against homologous and heterologous subgroup virus challenge.
The attachment glycoprotein G of respiratory syncytial (RS) virus is important in both the antigenic and molecular diversity of the RS viruses. Previous work has shown that the glycoprotein G of a subgroup A RS virus expressed from a recombinant vaccinia virus provides significant protection against homologous but not heterologous subgroup virus challenge. We undertook the cDNA cloning and nucleotide sequencing of the G mRNA of a subgroup B RS virus (8/60) to extend molecular comparisons of the G protein both within and between subgroups. We also tested the ability of a subgroup B G protein to provide protection against challenge by A or B subgroup viruses. Sequence analysis showed a deduced amino acid sequence having a single major open reading frame encoding a protein of 292 amino acids with an elevated serine and threonine (30%) and proline (9%) content. The 8/60 G differed from a subgroup A virus (A2) G protein with only a 56% amino acid identity while the 8/60 G shared a 98% amino acid identity with the G protein of another subgroup B virus (18537). The 8/60 G cDNA was placed in a vaccinia virus vector (vvGB) which was shown to express the 8/60 G protein. Cotton rats immunized intradermally with vvGB and later challenged intranasally with 8/60 RS virus had a significant reduction in viral titers in the lungs relative to control animals whereas similarly immunized animals were not protected against heterologous subgroup challenge. Our results indicate that a RS virus subunit vaccine containing the G protein would require both A and B subgroup G proteins to afford protection against viruses of both subgroups.
Sullender
W M
WM
Department of Microbiology, University of Alabama School of Medicine, Birmingham 35294.
Anderson
K
K
Wertz
G W
GW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D000939:Epitopes / Q000235:genetics; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D005814:Genes, Viral; D014644:Genetic Variation; D005822:Genetic Vectors; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012136:Respiratory Syncytial Viruses / Q000235:genetics*; D010253:Respirovirus Infections / Q000235:genetics; D014612:Vaccines; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
D000939:Epitopes; D006023:Glycoproteins; D012333:RNA, Messenger; D014612:Vaccines; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D019204:GTP-Binding Proteins