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. 1994 Jan;68(1):575–579. doi: 10.1128/jvi.68.1.575-579.1994

Use of random systematic mutagenesis to generate viable human rhinovirus 14 chimeras displaying human immunodeficiency virus type 1 V3 loop sequences.

A D Smith 1, D A Resnick 1, A Zhang 1, S C Geisler 1, E Arnold 1, G F Arnold 1
PMCID: PMC236325  PMID: 8254775

Abstract

Random systematic mutagenesis was used to generate a library of human rhinovirus 14 chimeras that each display a segment from the V3 loop of human immunodeficiency virus type 1. The sequence XXIGPGRAXX, where X could be any of the 20 amino acids, was inserted at the neutralizing immunogenic site II of human rhinovirus 14 between VP2 residues 159 and 160. Twenty-five unique chimeric viruses were isolated, and the identity of their randomized residues was determined. A nonrandom amino acid distribution that may reflect structural requirements for viability was observed at the randomized positions. Fifteen of 25 chimeras were neutralized by one or more of a panel of four anti-human immunodeficiency virus type 1 V3 loop antibody preparations, indicating that antigenicity had been successfully transplanted. Libraries of chimeric viruses produced by using the techniques described may be a source of vaccines and other immunotherapeutic reagents. The random systematic mutagenesis methodology described should be generally useful for the rapid transplantation of foreign sequences into viral coat and other proteins to produce libraries containing members with the desired properties.

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Selected References

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  1. Altmeyer R., Murdin A. D., Harber J. J., Wimmer E. Construction and characterization of a poliovirus/rhinovirus antigenic hybrid. Virology. 1991 Oct;184(2):636–644. doi: 10.1016/0042-6822(91)90433-c. [DOI] [PubMed] [Google Scholar]
  2. Arnold E., Rossmann M. G. Analysis of the structure of a common cold virus, human rhinovirus 14, refined at a resolution of 3.0 A. J Mol Biol. 1990 Feb 20;211(4):763–801. doi: 10.1016/0022-2836(90)90076-x. [DOI] [PubMed] [Google Scholar]
  3. Burke K. L., Evans D. J., Jenkins O., Meredith J., D'Souza E. D., Almond J. W. A cassette vector for the construction of antigen chimaeras of poliovirus. J Gen Virol. 1989 Sep;70(Pt 9):2475–2479. doi: 10.1099/0022-1317-70-9-2475. [DOI] [PubMed] [Google Scholar]
  4. Crabbe M. J., Evans D. J., Almond J. W. Modelling of poliovirus. HIV-1 antigen chimaeras. FEBS Lett. 1990 Oct 1;271(1-2):194–198. doi: 10.1016/0014-5793(90)80404-7. [DOI] [PubMed] [Google Scholar]
  5. Dedieu J. F., Ronco J., van der Werf S., Hogle J. M., Henin Y., Girard M. Poliovirus chimeras expressing sequences from the principal neutralization domain of human immunodeficiency virus type 1. J Virol. 1992 May;66(5):3161–3167. doi: 10.1128/jvi.66.5.3161-3167.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Evans D. J., McKeating J., Meredith J. M., Burke K. L., Katrak K., John A., Ferguson M., Minor P. D., Weiss R. A., Almond J. W. An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies. Nature. 1989 Jun 1;339(6223):385-8, 340. doi: 10.1038/339385a0. [DOI] [PubMed] [Google Scholar]
  7. Jenkins O., Cason J., Burke K. L., Lunney D., Gillen A., Patel D., McCance D. J., Almond J. W. An antigen chimera of poliovirus induces antibodies against human papillomavirus type 16. J Virol. 1990 Mar;64(3):1201–1206. doi: 10.1128/jvi.64.3.1201-1206.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kitson J. D., Burke K. L., Pullen L. A., Belsham G. J., Almond J. W. Chimeric polioviruses that include sequences derived from two independent antigenic sites of foot-and-mouth disease virus (FMDV) induce neutralizing antibodies against FMDV in guinea pigs. J Virol. 1991 Jun;65(6):3068–3075. doi: 10.1128/jvi.65.6.3068-3075.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. LaRosa G. J., Davide J. P., Weinhold K., Waterbury J. A., Profy A. T., Lewis J. A., Langlois A. J., Dreesman G. R., Boswell R. N., Shadduck P. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science. 1990 Aug 24;249(4971):932–935. doi: 10.1126/science.2392685. [DOI] [PubMed] [Google Scholar]
  10. Lemon S. M., Barclay W., Ferguson M., Murphy P., Jing L., Burke K., Wood D., Katrak K., Sangar D., Minor P. D. Immunogenicity and antigenicity of chimeric picornaviruses which express hepatitis A virus (HAV) peptide sequences: evidence for a neutralization domain near the amino terminus of VP1 of HAV. Virology. 1992 May;188(1):285–295. doi: 10.1016/0042-6822(92)90758-h. [DOI] [PubMed] [Google Scholar]
  11. London S. D., Schmaljohn A. L., Dalrymple J. M., Rice C. M. Infectious enveloped RNA virus antigenic chimeras. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):207–211. doi: 10.1073/pnas.89.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Masuda T., Matsushita S., Kuroda M. J., Kannagi M., Takatsuki K., Harada S. Generation of neutralization-resistant HIV-1 in vitro due to amino acid interchanges of third hypervariable env region. J Immunol. 1990 Nov 15;145(10):3240–3246. [PubMed] [Google Scholar]
  13. Mizutani S., Colonno R. J. In vitro synthesis of an infectious RNA from cDNA clones of human rhinovirus type 14. J Virol. 1985 Nov;56(2):628–632. doi: 10.1128/jvi.56.2.628-632.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Murray M. G., Kuhn R. J., Arita M., Kawamura N., Nomoto A., Wimmer E. Poliovirus type 1/type 3 antigenic hybrid virus constructed in vitro elicits type 1 and type 3 neutralizing antibodies in rabbits and monkeys. Proc Natl Acad Sci U S A. 1988 May;85(9):3203–3207. doi: 10.1073/pnas.85.9.3203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ohno T., Terada M., Yoneda Y., Shea K. W., Chambers R. F., Stroka D. M., Nakamura M., Kufe D. W. A broadly neutralizing monoclonal antibody that recognizes the V3 region of human immunodeficiency virus type 1 glycoprotein gp120. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10726–10729. doi: 10.1073/pnas.88.23.10726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Reimann B. Y., Zell R., Kandolf R. Mapping of a neutralizing antigenic site of Coxsackievirus B4 by construction of an antigen chimera. J Virol. 1991 Jul;65(7):3475–3480. doi: 10.1128/jvi.65.7.3475-3480.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rossmann M. G., Arnold E., Erickson J. W., Frankenberger E. A., Griffith J. P., Hecht H. J., Johnson J. E., Kamer G., Luo M., Mosser A. G. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature. 1985 Sep 12;317(6033):145–153. doi: 10.1038/317145a0. [DOI] [PubMed] [Google Scholar]
  18. Sherry B., Mosser A. G., Colonno R. J., Rueckert R. R. Use of monoclonal antibodies to identify four neutralization immunogens on a common cold picornavirus, human rhinovirus 14. J Virol. 1986 Jan;57(1):246–257. doi: 10.1128/jvi.57.1.246-257.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sherry B., Rueckert R. Evidence for at least two dominant neutralization antigens on human rhinovirus 14. J Virol. 1985 Jan;53(1):137–143. doi: 10.1128/jvi.53.1.137-143.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wang C. Y., Looney D. J., Li M. L., Walfield A. M., Ye J., Hosein B., Tam J. P., Wong-Staal F. Long-term high-titer neutralizing activity induced by octameric synthetic HIV-1 antigen. Science. 1991 Oct 11;254(5029):285–288. doi: 10.1126/science.254.5029.285. [DOI] [PubMed] [Google Scholar]

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