This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tanabe, H. Articles by Robinson, W. E. Search for Related Content PubMed PubMed Citation Articles by Tanabe, H. Articles by Robinson, W. E., Jr. Pubmed/NCBI databases Substance via MeSH

 Previous Article  |  Next Article 

Journal of Virology, November 2004, p. 11622-11631, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11622-11631.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Differential Effects on Human Immunodeficiency Virus Type 1 Replication by -Defensins with Comparable Bactericidal Activities

Hiroki Tanabe,¹ Andre J. Ouellette,^1,2 Melanie J. Cocco,³ and W. Edward Robinson Jr.^1,2*

Departments of Pathology,¹ Microbiology and Molecular Genetics,² Molecular Biology and Biochemistry, University of California, Irvine, California³

Received 29 August 2003/ Accepted 29 June 2004

In addition to their antibacterial activities, certain antimicrobial peptides inactivate enveloped viruses, including the human immunodeficiency virus (HIV). To determine whether peptide bactericidal activities are predictive of antiviral activity, the anti-HIV properties of recombinant human -defensin 5, mouse -defensins, cryptdins (Crp) 3 and 4, and rhesus macaque myeloid -defensins (RMADs) 3 and 4 were determined in vitro. The peptides, purified to homogeneity, had equivalent bactericidal activities that were similar to those of the native molecules. Nuclear magnetic resonance spectroscopy showed RMAD-4 and Crp3 had characteristic -defensin tridisulfide arrays. Of the peptides analyzed, only RMAD-4 inhibited HIV infectivity at 150 µg/ml, and Crp3 unexpectedly increased HIV replication. Quantitative real-time PCRs for minus-strand strong stop DNA and complete viral cDNA synthesis were used to distinguish between preentry and postentry anti-HIV effects by RMAD-4. Viral exposure to RMAD-4 for 1 h prior to infection reduced HIV minus-strand strong stop DNA and HIV cDNA by 4- to 20-fold during the first round of replication, showing that RMAD-4-exposed virions were not entering cells during the first 24 h. On the other hand, when RMAD-4 was added coincident with HIV inoculation, no anti-HIV activity was detected. Viral exposure to Crp3 resulted in a threefold increase in both HIV minus-strand strong stop DNA and HIV cDNA over the first round of replication. Therefore, two -defensins, RMAD-4 and Crp3, inhibit or augment HIV replication, respectively, by mechanisms that precede reverse transcription.

---

* Corresponding author. Mailing address: Department of Pathology, D440 Med Sci I, University of California, Irvine, CA 92697-4800. Phone: (949) 824-3431. Fax: (949) 824-2505. E-mail: ewrobins{at}uci.edu.

---

Journal of Virology, November 2004, p. 11622-11631, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11622-11631.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Llenado, R. A., Weeks, C. S., Cocco, M. J., Ouellette, A. J. (2009). Electropositive Charge in {alpha}-Defensin Bactericidal Activity: Functional Effects of Lys-for-Arg Substitutions Vary with the Peptide Primary Structure. Infect. Immun. 77: 5035-5043 [Abstract] [Full Text]  
• Kamdar, K., Maemoto, A., Qu, X., Young, S. K., Ouellette, A. J. (2008). In Vitro Activation of the Rhesus Macaque Myeloid {alpha}-Defensin Precursor proRMAD-4 by Neutrophil Serine Proteinases. J. Biol. Chem. 283: 32361-32368 [Abstract] [Full Text]  
• Diamond, G., Beckloff, N., Ryan, L.K. (2008). Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences. JDR 87: 915-927 [Abstract] [Full Text]  
• Klotman, M. E., Rapista, A., Teleshova, N., Micsenyi, A., Jarvis, G. A., Lu, W., Porter, E., Chang, T. L. (2008). Neisseria gonorrhoeae-Induced Human Defensins 5 and 6 Increase HIV Infectivity: Role in Enhanced Transmission. J. Immunol. 180: 6176-6185 [Abstract] [Full Text]  
• Brandt, C. R., Akkarawongsa, R., Altmann, S., Jose, G., Kolb, A. W., Waring, A. J., Lehrer, R. I. (2007). Evaluation of a {theta}-Defensin in a Murine Model of Herpes Simplex Virus Type 1 Keratitis. IOVS 48: 5118-5124 [Abstract] [Full Text]  
• Furci, L., Sironi, F., Tolazzi, M., Vassena, L., Lusso, P. (2007). {alpha}-defensins block the early steps of HIV-1 infection: interference with the binding of gp120 to CD4. Blood 109: 2928-2936 [Abstract] [Full Text]  
• Groot, F., Sanders, R. W., ter Brake, O., Nazmi, K., Veerman, E. C. I., Bolscher, J. G. M., Berkhout, B. (2006). Histatin 5-derived Peptide with improved fungicidal properties enhances human immunodeficiency virus type 1 replication by promoting viral entry.. J. Virol. 80: 9236-9243 [Abstract] [Full Text]  
• Moutsopoulos, N.M., Greenwell-Wild, T., Wahl, S.M. (2006). Differential Mucosal Susceptibility in HIV-1 Transmission and Infection. ADR 19: 52-56 [Abstract] [Full Text]  
• VanCompernolle, S. E., Taylor, R. J., Oswald-Richter, K., Jiang, J., Youree, B. E., Bowie, J. H., Tyler, M. J., Conlon, J. M., Wade, D., Aiken, C., Dermody, T. S., KewalRamani, V. N., Rollins-Smith, L. A., Unutmaz, D. (2005). Antimicrobial Peptides from Amphibian Skin Potently Inhibit Human Immunodeficiency Virus Infection and Transfer of Virus from Dendritic Cells to T Cells. J. Virol. 79: 11598-11606 [Abstract] [Full Text]