Human defensins, aptly named antimicrobial peptides, are made in immune system cells and epithelial cells (such as skin cells and cells that line the gut). One of these peptides, human neutrophil peptide 1, under certain circumstances hinders HIV infection, but exactly how it works remains unclear.
HIV entry into mature T-helper cells (cells essential to the immune system) proceeds by attachment of the virus to specific targets on T-helper cells, uptake of the virus, fusion of its envelope with the cell membranes, and release of the virus into the cells. In a forthcoming Journal of Biological Chemistry Paper of the Week, Gregory Melikyan at Emory University and colleagues investigated the ability of human neutrophil peptide 1 to impede each step of this process.
Using model cell lines, Melikyan's group showed that human neutrophil peptide 1 effectively prevented HIV entry into cells in multiple ways. First, human neutrophil peptide 1 reduced the number of specific targets on the cells available for HIV attachment. Second, this defensin also bound to specific targets on both the HIV envelope and the cells, preventing early and late stages of HIV-cell fusion. Finally, human neutrophil peptide 1 prevented HIV uptake into the cells without compromising the general ability of the cells to engulf other molecules.
While human neutrophil peptide 1 hinders HIV entry into cells under these lab conditions, it does not do so as effectively in the presence of serum -- meaning that it may not be as successful at blocking HIV in our bodies. But Melikyan's team showed that human neutrophil peptide 1 remained attached to its specific targets in the presence of serum, despite its reduced efficacy. Their work suggests that the structure of human neutrophil peptide 1 is important for its anti-HIV activity, and they propose that serum may interfere with the ability of this defensin to form complexes, reducing its ability to block HIV.
"Our work provides new insights into the ability of defensins to recognize and neutralize diverse pathogens, including HIV," Melikyan says. This research reveals that human neutrophil peptide 1 can bind various viral and cellular targets and that a previously unappreciated feature is essential for its anti-HIV activity, possibly its propensity to form large complexes, Melikyan explains.
The team's findings suggest a new avenue of research for combatting HIV and viruses that infiltrate cells in a similar manner.
From the article: "Multifaceted mechanisms of HIV-1 entry inhibition by human alpha-defensin" by Lusine H. Demirkhanyan, Mariana Marin, Sergi Padilla-Parra, Changyou Zhan, Kosuke Miyauchi, Maikha Jean-Baptiste, Gennadiy Novitskiy, Wuyuan Lu, and Gregory B. Melikyan (to be published in the Aug. 17 issue of the Journal of Biological Chemistry and currently online as a Paper in Press at http://www.jbc.org/content/early/2012/06/25/jbc.M112.375949.full.pdf)
Corresponding author: Gregory B. Melikyan, Department of Pediatrics Infectious Diseases, Emory University in Atlanta, GA, USA; email: email@example.com
Written by Danielle Gutierrez
Angela Hopp | EurekAlert!
Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo
Full of hot air and proud of it
18.04.2018 | University of Pittsburgh
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.
Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
19.04.2018 | Materials Sciences
19.04.2018 | Physics and Astronomy
19.04.2018 | Physics and Astronomy