A Cellular "Armor" Offers Hope for Combating HIV/AIDS

The HIV/AIDS pandemic is arguably one of the worst health crises in recent history, accounting for the premature deaths and disabilities of millions of individuals across the globe. Since 1981, AIDS (Acquired Immune Deficiency Syndrome) has killed over 25 million people and remains among the top five leading causes of mortality worldwide (1). Moreover, it is estimated that 33.4 million individuals are currently infected with HIV and approximately 2.7 million people are becoming newly infected each year (2). Given the enormous social and economic impact of HIV/AIDS, scientists across the world have been hard at work to fight and cure this disease. A recent finding reported in the Cell Press Journal of Chemistry & Biology offers hope for a novel strategy in preventing entry of the HIV virus into host cells, thereby halting disease progression.

In the study, which was led by Felix Goñi at La Universidad del País Vasco in Spain, the researchers focused on the mechanism by which the HIV (human immunodeficiency virus) virus enters the host cell (3). For viruses to infect human cells, their membranes must bind to receptors on the host's cell surface. As a result of this membrane fusion, the virus is able to enter the host cell, replicate, assemble new viral particles, and infect more host cells upon lysogenesis. Lysogenesis is the process by which the host cell lyses, consequently releasing the viral particles into the surroundings. This entire process ultimately leads to a weakened immune system and a progression to AIDS.

The researchers found that inhibition of a protein called Des1, found on human cell surfaces, leads to increasing levels of dihydrosphingomyelin (DHSM), which is a component of human cell membranes. Increased levels of DHSM, in turn, introduces more rigidity to the cell membrane, a trait that prevents fusion with the HIV viral membrane and thereby inhibits viral entry into the host cell. Thus, by making an otherwise fluid membrane more rigid, it is possible to halt the progress of the virus even before it enters the host cell. This discovery offers a novel route to treatment distinct from existing therapies that focus on blocking replication after cellular infection.

As Goñi pointed out, "There is medication, which is working well, to avoid the propagation of the virus once it is inside the cell.but this drug is based on a completely distinct principle. The idea of modifying the rigidity of the membranes is completely new and.by equipping these membranes with greater rigidity, the AIDS virus cannot penetrate" (4). Thus, unlike the current antiretroviral treatments that prevents the progression of HIV-infection into full-blown AIDS, this cellular "armor" would inhibit HIV infection of host cells altogether. These findings offer insight into potentially more effective and less costly means of combating the global HIV/AIDS pandemic.

References:

(1) The Global Fund to Fight AIDS, Tuberculosis and Malaria. "HIV/AIDS Background". http://www.theglobalfund.org/en/hivaids/background/

(2) AVERT HIV and AIDS. "Global HIV/AIDS Estimates". http://www.avert.org/worldstats.htm

(3) Viera, CR, et al. (2010) "Dihydrosphingomyelin Impairs HIV-1 Infection by Rigidifying Liquid-Ordered Membrane Domains". Chemistry & Biology 17(7): 766-775.

(4) ScienceBlog. "New armor' developed to avoid infection from AIDS virus". http://scienceblog.com/37063/new-armor-developed-to-avoid-infection-from-aids-virus/

Author: Eanas Aboobaker

Reviewed by: Jessica Kloss, Natasha Hochlowski, and Yangguang Ou

Published by: Maria Huang

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