Design and construction of rhinovirus chimeras incorporating immunogens from polio, influenza, and human immunodeficiency viruses.
This paper describes the design and construction of chimeric human rhinoviruses that contain immunogenic regions from other pathogens as part of their surface coat proteins. Segments encoding the poliovirus 3 Sabin VP1 and VP2 proteins, the influenza hemagglutinin (HA) glycoprotein, and the human immunodeficiency virus gp120 surface and gp41 transmembrane glycoproteins were inserted into a full-length clone of human rhinovirus 14 (HRV14) at regions corresponding to neutralizing immunogenic sites IA (NIm-IA) and II (NIm-II). Of 12 chimeric constructs described, 3 produced viable virus. An HRV14 chimeric virus containing five amino acids of influenza HA (corresponding to 300 A2 of solvent-accessible surface area) had wild-type HRV14 growth characteristics and was neutralized by four of four anti-influenza HA antisera with reciprocal neutralizing titers ranging from 180 to 330. However, antisera raised in two guinea pigs against the HRV14:influenza HA chimera did not show significant neutralization of relevant strains of influenza. These results are the first to demonstrate the feasibility of making viable chimeras of human rhinoviruses displaying heterologous immunogens.
Arnold
G F
GF
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854.
Resnick
D A
DA
Li
Y
Y
Zhang
A
A
Smith
A D
AD
Geisler
S C
SC
Jacobo-Molina
A
A
Lee
W
W
Webster
R G
RG
Arnold
E
E
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002213:Capsid / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D000939:Epitopes / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017955:Poliovirus / Q000235:genetics / Q000276:immunology; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012229:Rhinovirus / Q000235:genetics* / Q000254:growth & development
D000956:Antigens, Viral; D036022:Capsid Proteins; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D011993:Recombinant Fusion Proteins; C442540:VP1 protein, Poliovirus; C442541:VP2 protein, Poliovirus; C442544:VP2 protein, Rhinovirus