Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Oct 11;91(21):9775–9779. doi: 10.1073/pnas.91.21.9775

Attenuated Mengo virus as a vector for immunogenic human immunodeficiency virus type 1 glycoprotein 120.

R Altmeyer 1, N Escriou 1, M Girard 1, A Palmenberg 1, S van der Werf 1
PMCID: PMC44899  PMID: 7937890

Abstract

Introduction of a sequence encoding 147 amino acids from human immunodeficiency virus type I (HIV-1) strain MN glycoprotein gp120 into the RNA genome of the stably attenuated Mengo virus strain vM16 yielded an infectious recombinant virus, vMLN450, which expressed the heterologous HIV-1 sequence along with the normal Mengo virus proteins. The HIV-1 gp120 sequence, fused to the amino terminus of the short, nonstructural Mengo virus leader polypeptide was recognized by a gp120 V3 loop-specific monoclonal antibody. When inoculated into mice, recombinant virus vMLN450 elicited a high-titer anti-HIV-1 antibody response as well as an HIV-1MN-specific cytotoxic cellular immune response. An anti-HIV-1 antibody response could also be detected in cynomolgus monkeys after a single immunization. We propose that attenuated Mengo virus can serve as an effective expression vector in cell systems and various animal species and offers another approach to the development of new, live recombinant vaccines.

Full text

PDF
9776

Images in this article

9776Image
on p.9776
9776Image
on p.9776
9777Image
on p.9777

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander L., Lu H. H., Wimmer E. Polioviruses containing picornavirus type 1 and/or type 2 internal ribosomal entry site elements: genetic hybrids and the expression of a foreign gene. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1406–1410. doi: 10.1073/pnas.91.4.1406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Duke G. M., Osorio J. E., Palmenberg A. C. Attenuation of Mengo virus through genetic engineering of the 5' noncoding poly(C) tract. Nature. 1990 Feb 1;343(6257):474–476. doi: 10.1038/343474a0. [DOI] [PubMed] [Google Scholar]
  5. Duke G. M., Palmenberg A. C. Cloning and synthesis of infectious cardiovirus RNAs containing short, discrete poly(C) tracts. J Virol. 1989 Apr;63(4):1822–1826. doi: 10.1128/jvi.63.4.1822-1826.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Emini E. A., Jameson B. A., Lewis A. J., Larsen G. R., Wimmer E. Poliovirus neutralization epitopes: analysis and localization with neutralizing monoclonal antibodies. J Virol. 1982 Sep;43(3):997–1005. doi: 10.1128/jvi.43.3.997-1005.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Harber J. J., Bradley J., Anderson C. W., Wimmer E. Catalysis of poliovirus VP0 maturation cleavage is not mediated by serine 10 of VP2. J Virol. 1991 Jan;65(1):326–334. doi: 10.1128/jvi.65.1.326-334.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Helwig F. C., Schmidt C. H. A FILTER-PASSING AGENT PRODUCING INTERSTITIAL MYOCARDITIS IN ANTHROPOID APES AND SMALL ANIMALS. Science. 1945 Jul 13;102(2637):31–33. doi: 10.1126/science.102.2637.31. [DOI] [PubMed] [Google Scholar]
  9. Hubbard G. B., Soike K. F., Butler T. M., Carey K. D., Davis H., Butcher W. I., Gauntt C. J. An encephalomyocarditis virus epizootic in a baboon colony. Lab Anim Sci. 1992 Jun;42(3):233–239. [PubMed] [Google Scholar]
  10. Jang S. K., Kräusslich H. G., Nicklin M. J., Duke G. M., Palmenberg A. C., Wimmer E. A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J Virol. 1988 Aug;62(8):2636–2643. doi: 10.1128/jvi.62.8.2636-2643.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Karzon D. T., Bolognesi D. P., Koff W. C. Development of a vaccine for the prevention of AIDS, a critical appraisal. Vaccine. 1992;10(14):1039–1052. doi: 10.1016/0264-410x(92)90114-y. [DOI] [PubMed] [Google Scholar]
  12. Kaufman R. J., Davies M. V., Wasley L. C., Michnick D. Improved vectors for stable expression of foreign genes in mammalian cells by use of the untranslated leader sequence from EMC virus. Nucleic Acids Res. 1991 Aug 25;19(16):4485–4490. doi: 10.1093/nar/19.16.4485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Martin A., Wychowski C., Couderc T., Crainic R., Hogle J., Girard M. Engineering a poliovirus type 2 antigenic site on a type 1 capsid results in a chimaeric virus which is neurovirulent for mice. EMBO J. 1988 Sep;7(9):2839–2847. doi: 10.1002/j.1460-2075.1988.tb03140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Palmenberg A. C. Proteolytic processing of picornaviral polyprotein. Annu Rev Microbiol. 1990;44:603–623. doi: 10.1146/annurev.mi.44.100190.003131. [DOI] [PubMed] [Google Scholar]
  15. Parks G. D., Duke G. M., Palmenberg A. C. Encephalomyocarditis virus 3C protease: efficient cell-free expression from clones which link viral 5' noncoding sequences to the P3 region. J Virol. 1986 Nov;60(2):376–384. doi: 10.1128/jvi.60.2.376-384.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pelletier J., Sonenberg N. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature. 1988 Jul 28;334(6180):320–325. doi: 10.1038/334320a0. [DOI] [PubMed] [Google Scholar]
  17. Rey F., Barré-Sinoussi F., Schmidtmayerova H., Chermann J. C. Detection and titration of neutralizing antibodies to HIV using an inhibition of the cytopathic effect of the virus on MT4 cells. J Virol Methods. 1987 Jun;16(3):239–249. doi: 10.1016/0166-0934(87)90008-5. [DOI] [PubMed] [Google Scholar]
  18. Smith A. D., Resnick D. A., Zhang A., Geisler S. C., Arnold E., Arnold G. F. Use of random systematic mutagenesis to generate viable human rhinovirus 14 chimeras displaying human immunodeficiency virus type 1 V3 loop sequences. J Virol. 1994 Jan;68(1):575–579. doi: 10.1128/jvi.68.1.575-579.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Takahashi H., Merli S., Putney S. D., Houghten R., Moss B., Germain R. N., Berzofsky J. A. A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160. Science. 1989 Oct 6;246(4926):118–121. doi: 10.1126/science.2789433. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES