Skip to main content
NCBI 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
. 1993 Oct 1;90(19):9140–9144. doi: 10.1073/pnas.90.19.9140

Replication-incompetent herpesvirus vector delivery of an interferon alpha gene inhibits human immunodeficiency virus replication in human monocytes.

J P Weir 1, K L Elkins 1
PMCID: PMC47517  PMID: 8415668

Abstract

Human monocytes and macrophages are nondividing cells that serve as a major reservoir for human immunodeficiency virus (HIV) at all stages of infection. To investigate viral-mediated gene delivery as a means of inhibiting HIV replication in human monocytes, a replication-incompetent herpes simplex virus vector was developed that expressed human interferon alpha. Monocytes infected with this herpes simplex virus vector and then challenged with HIV showed dramatically reduced cytopathic effects and HIV replication compared to control treated monocytes. Similar effects on HIV replication were observed if monocytes were first infected with HIV and then treated with the recombinant vectors. These results demonstrate that replication-incompetent herpes simplex virus gene delivery of interferon alpha directly to human monocytes can greatly decrease HIV replication and suggest that such a vector might deliver therapeutically important genes directly to sites of HIV infection.

Full text

PDF
9140

Images in this article

9141Fig. 1
on p.9141
9142Fig. 2
on p.9142
9143Fig. 3
on p.9143

Selected References

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

  1. Albrecht M. A., DeLuca N. A., Byrn R. A., Schaffer P. A., Hammer S. M. The herpes simplex virus immediate-early protein, ICP4, is required to potentiate replication of human immunodeficiency virus in CD4+ lymphocytes. J Virol. 1989 May;63(5):1861–1868. doi: 10.1128/jvi.63.5.1861-1868.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Breakefield X. O., DeLuca N. A. Herpes simplex virus for gene delivery to neurons. New Biol. 1991 Mar;3(3):203–218. [PubMed] [Google Scholar]
  3. Culver K., Cornetta K., Morgan R., Morecki S., Aebersold P., Kasid A., Lotze M., Rosenberg S. A., Anderson W. F., Blaese R. M. Lymphocytes as cellular vehicles for gene therapy in mouse and man. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3155–3159. doi: 10.1073/pnas.88.8.3155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DeLuca N. A., McCarthy A. M., Schaffer P. A. Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. J Virol. 1985 Nov;56(2):558–570. doi: 10.1128/jvi.56.2.558-570.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DeLuca N. A., Schaffer P. A. Activities of herpes simplex virus type 1 (HSV-1) ICP4 genes specifying nonsense peptides. Nucleic Acids Res. 1987 Jun 11;15(11):4491–4511. doi: 10.1093/nar/15.11.4491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Friedmann T. Progress toward human gene therapy. Science. 1989 Jun 16;244(4910):1275–1281. doi: 10.1126/science.2660259. [DOI] [PubMed] [Google Scholar]
  7. Gendelman H. E., Baca L. M., Turpin J., Kalter D. C., Hansen B., Orenstein J. M., Dieffenbach C. W., Friedman R. M., Meltzer M. S. Regulation of HIV replication in infected monocytes by IFN-alpha. Mechanisms for viral restriction. J Immunol. 1990 Oct 15;145(8):2669–2676. [PubMed] [Google Scholar]
  8. Gendelman H. E., Orenstein J. M., Martin M. A., Ferrua C., Mitra R., Phipps T., Wahl L. A., Lane H. C., Fauci A. S., Burke D. S. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J Exp Med. 1988 Apr 1;167(4):1428–1441. doi: 10.1084/jem.167.4.1428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Johnson P. A., Miyanohara A., Levine F., Cahill T., Friedmann T. Cytotoxicity of a replication-defective mutant of herpes simplex virus type 1. J Virol. 1992 May;66(5):2952–2965. doi: 10.1128/jvi.66.5.2952-2965.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kornbluth R. S., Oh P. S., Munis J. R., Cleveland P. H., Richman D. D. Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro. J Exp Med. 1989 Mar 1;169(3):1137–1151. doi: 10.1084/jem.169.3.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lane H. C., Davey V., Kovacs J. A., Feinberg J., Metcalf J. A., Herpin B., Walker R., Deyton L., Davey R. T., Jr, Falloon J. Interferon-alpha in patients with asymptomatic human immunodeficiency virus (HIV) infection. A randomized, placebo-controlled trial. Ann Intern Med. 1990 Jun 1;112(11):805–811. doi: 10.7326/0003-4819-112-11-805. [DOI] [PubMed] [Google Scholar]
  12. Maeda S., McCandliss R., Gross M., Sloma A., Familletti P. C., Tabor J. M., Evinger M., Levy W. P., Pestka S. Construction and identification of bacterial plasmids containing nucleotide sequence for human leukocyte interferon. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7010–7013. doi: 10.1073/pnas.77.12.7010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Meltzer M. S., Skillman D. R., Gomatos P. J., Kalter D. C., Gendelman H. E. Role of mononuclear phagocytes in the pathogenesis of human immunodeficiency virus infection. Annu Rev Immunol. 1990;8:169–194. doi: 10.1146/annurev.iy.08.040190.001125. [DOI] [PubMed] [Google Scholar]
  14. Meuret G., Hoffmann G. Monocyte kinetic studies in normal and disease states. Br J Haematol. 1973 Mar;24(3):275–285. doi: 10.1111/j.1365-2141.1973.tb01652.x. [DOI] [PubMed] [Google Scholar]
  15. Mosca J. D., Bednarik D. P., Raj N. B., Rosen C. A., Sodroski J. G., Haseltine W. A., Hayward G. S., Pitha P. M. Activation of human immunodeficiency virus by herpesvirus infection: identification of a region within the long terminal repeat that responds to a trans-acting factor encoded by herpes simplex virus 1. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7408–7412. doi: 10.1073/pnas.84.21.7408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Riches D. W., Henson P. M. Functional aspects of mononuclear phagocyte involvement in lung inflammation. Ann N Y Acad Sci. 1986;465:6–14. doi: 10.1111/j.1749-6632.1986.tb18475.x. [DOI] [PubMed] [Google Scholar]
  17. Rooney J. F., Wohlenberg C., Cremer K. J., Moss B., Notkins A. L. Immunization with a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: long-term protection and effect of revaccination. J Virol. 1988 May;62(5):1530–1534. doi: 10.1128/jvi.62.5.1530-1534.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rosenfeld M. A., Siegfried W., Yoshimura K., Yoneyama K., Fukayama M., Stier L. E., Päkkö P. K., Gilardi P., Stratford-Perricaudet L. D., Perricaudet M. Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science. 1991 Apr 19;252(5004):431–434. doi: 10.1126/science.2017680. [DOI] [PubMed] [Google Scholar]
  19. Weir J. P., Meltzer M. S. Transfection of human immunodeficiency virus type 1 proviral DNA into primary human monocytes. Cell Immunol. 1993 Apr 15;148(1):157–165. doi: 10.1006/cimm.1993.1098. [DOI] [PubMed] [Google Scholar]
  20. Weir J. P., Narayanan P. R. Expression of the herpes simplex virus type 1 glycoprotein C gene requires sequences in the 5' noncoding region of the gene. J Virol. 1990 Jan;64(1):445–449. doi: 10.1128/jvi.64.1.445-449.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Weir J. P., Narayanan P. R. The use of beta-galactosidase as a marker gene to define the regulatory sequences of the herpes simplex virus type 1 glycoprotein C gene in recombinant herpesviruses. Nucleic Acids Res. 1988 Nov 11;16(21):10267–10282. doi: 10.1093/nar/16.21.10267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weir J. P., Steffy K. R., Sethna M. An insertion vector for the analysis of gene expression during herpes simplex virus infection. Gene. 1990 May 14;89(2):271–274. doi: 10.1016/0378-1119(90)90016-k. [DOI] [PubMed] [Google Scholar]
  23. Whitelaw D. M. Observations on human monocyte kinetics after pulse labeling. Cell Tissue Kinet. 1972 Jul;5(4):311–317. doi: 10.1111/j.1365-2184.1972.tb00369.x. [DOI] [PubMed] [Google Scholar]
  24. van Furth R., Sluiter W., van Dissel J. T. Genetic control of macrophage responses. Ann N Y Acad Sci. 1986;465:15–25. doi: 10.1111/j.1749-6632.1986.tb18476.x. [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