Anti-HIV Activity of Human Defensin 5 in Primary CD4+ T Cells under Serum-Deprived Conditions Is a Consequence of Defensin-Mediated Cytotoxicity

Jian Ding, Carley Tasker, Kimyata Valere, Tiina Sihvonen, Dante B. Descalzi-Montoya, Wuyuan Lu, Theresa L. Chang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background:We have previously shown that human defensin 5 (HD5) promotes HIV infectivity in both primary CD4+ T cells and HeLa cells expressing CD4 and CCR5. HD5 is induced in response to sexually transmitted infections (STIs) such as Chlamydia trachomatis and Neisseria gonorrhoeae, suggesting it plays a role in STI-mediated enhancement of HIV transmission. In contrast to our findings, a recent study reports that HD5 has an anti-HIV effect in primary CD4+ T cells under serum-deprived conditions. To resolve these apparently contradictory observations, we investigated experimental parameters that might contribute to contrasting effects of HD5.Results:Serum-deprived culture conditions were associated with anti-HIV activity. In contrast to the dependence of the HIV enhancing effect on HD5 structure, the anti-HIV activity in serum-deprived primary CD4+ T cells was independent of HD5 structure as the linear peptide [Abu] HD5 exhibited similar anti-HIV activity. Under serum deprived conditions, HD5 blocked CD4-receptor-independent HIV-1vsv infection before or after viral entry. We found that HD5 and its linear form induced significant cell death in primary CD4+ T cells under serum-deprived culture conditions. HD5-mediated apoptosis was observed as early as 2 h after addition of defensins to serum-deprived primary CD4+ T cells. In contrast to primary CD4+ T cells, HD5 did not induce cytotoxicity and promote HIV infectivity of HeLa-CD4-CCR5 cells under serum-deprived conditions.Conclusions:These results indicate that under serum-deprived culture conditions HD5 is toxic for primary CD4+ T cells, warranting caution in data interpretation.

Original languageEnglish (US)
Article numbere76038
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 25 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint

Dive into the research topics of 'Anti-HIV Activity of Human Defensin 5 in Primary CD4+ T Cells under Serum-Deprived Conditions Is a Consequence of Defensin-Mediated Cytotoxicity'. Together they form a unique fingerprint.

Cite this