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: firstname.lastname@example.org
Written by Danielle Gutierrez
Angela Hopp | EurekAlert!
Monitoring biodiversity with sound: how machines can enrich our knowledge
18.06.2019 | Georg-August-Universität Göttingen
Uncovering hidden protein structures
18.06.2019 | Universität Konstanz
The well-known representation of chemical elements is just one example of how objects can be arranged and classified
The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...
Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.
Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...
Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.
The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...
Discovery by Brazilian and US researchers could change the classification of two species, which appear more akin to jellyfish than was thought.
The tube anemone Isarachnanthus nocturnus is only 15 cm long but has the largest mitochondrial genome of any animal sequenced to date, with 80,923 base pairs....
Researchers at Chalmers University of Technology, Sweden, have discovered a completely new way of capturing, amplifying and linking light to matter at the nanolevel. Using a tiny box, built from stacked atomically thin material, they have succeeded in creating a type of feedback loop in which light and matter become one. The discovery, which was recently published in Nature Nanotechnology, opens up new possibilities in the world of nanophotonics.
Photonics is concerned with various means of using light. Fibre-optic communication is an example of photonics, as is the technology behind photodetectors and...
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
18.06.2019 | Life Sciences
18.06.2019 | Life Sciences
18.06.2019 | Life Sciences