Under the right conditions, peptide blocks HIV infection at multiple points along the way

July 24, 2012 by Danielle Gutierrez

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- (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 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 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-. 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.

Explore further: Entry prohibited for AIDS viruses: Peptide triazole inhibitors disrupt cell-free HIV-1

More information: "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 www.jbc.org/content/early/2012 … M112.375949.full.pdf )

Related Stories

Entry prohibited for AIDS viruses: Peptide triazole inhibitors disrupt cell-free HIV-1

July 8, 2011
(PhysOrg.com) -- The initial entry of HIV-1 into host cells remains a compelling yet elusive target for the development of agents to prevent infection, a critical need in the fight against the global AIDS epidemic.

Step in breakdown of HIV proteins essential to recognition, destruction of infected cells

May 9, 2011
A key step in the processing of HIV within cells appears to affect how effectively the immune system's killer T cells can recognize and destroy infected cells. Researchers at the Ragon Institute of MGH, MIT and Harvard have ...

Mechanism of HIV spread has potential for future drug therapy

April 23, 2012
A new understanding of the initial interactions of human immunodeficiency virus type 1 (HIV-1) and dendritic cells is described by Boston University School of Medicine (BUSM) researchers in a study currently featured in the ...

New memory for HIV patients

March 26, 2012
The hallmark loss of helper CD4+ T cells during human immunodeficiency virus (HIV) infection may be a red herring for therapeutics, according to a study published on March 26th in the Journal of Experimental Medicine.

Recommended for you

Study suggests a way to stop HIV in its tracks

December 1, 2017
When HIV-1 infects an immune cell, the virus travels to the nucleus so quickly there's not enough time to set off the cell's alarm system.

Discovery puts the brakes on HIV's ability to infect

November 30, 2017
Viewed with a microscope, the virus faintly resembles a pineapple—the universal symbol of welcome. But HIV, the virus that causes AIDS, is anything but that. It has claimed the lives of more than 35 million people so far.

Rising levels of HIV drug resistance

November 30, 2017
HIV drug resistance is approaching and exceeding 10% in people living with HIV who are about to initiate or reinitiate first-line antiretroviral therapy, according to the largest meta-analysis to date on HIV drug resistance, ...

Male circumcision and antiviral drugs appear to sharply reduce HIV infection rate

November 29, 2017
A steep drop in the local incidence of new HIV infections accompanied the rollout of a U.S.-funded anti-HIV program in a large East-African population, according to a study led by researchers at Johns Hopkins Bloomberg School ...

Combination HIV prevention reduces new infections by 42 percent in Ugandan district

November 29, 2017
A study published today in the New England Journal of Medicine provides real-world evidence that implementing a combination of proven HIV prevention measures across communities can substantially reduce new HIV infections ...

Research on HIV viral load urges updates to WHO therapy guidelines

November 24, 2017
A large cohort study in South Africa has revealed that that low-level viraemia (LLV) in HIV-positive patients who are receiving antiretroviral treatment (ART) is an important risk factor for treatment failure.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.