Decoy protein stops all tested HIV strains

Posted: February 19, 2015 at 9:41 am

How HIV infects a CD4+ T-helper cell. (1) The gp120 viral protein attaches to CD4. (2) The gp120 variable loop attaches to a coreceptor, either CCR5 or CXCR4. (3) HIV enters the cell.

Ever since HIV emerged as a deadly public health threat in the early 1980s, scientists have sought a vaccine that could repel the virus and prevent AIDS. Three decades of intensive research have come up short, although drugs to treat HIV infection have transformed the disease from a death sentence to a chronic disease people can live with.

However, in Third World countries where access to HIV drugs is limited, HIV continues to devastate populations. That could change, if a new study led by scientists from The Scripps Research Institute lives up to its promise.

The scientists have created a genetically engineered protein that inactivates virtually all strains of the virus. While it will take years before this approach can be tested in humans, the concept provides a fresh insight on how to protect people against infection from the AIDS-causing virus.

The protein mimics two receptors on the surface of the immune cells that HIV infects. When the virus encounters the protein, it springs into action as if infecting a cell. The changes the virus undergoes render it incapable of future attempts at infection, said Michael Farzan, a Scripps Research scientist who led the study.

The protein neutralized 100 percent of neutralization-resistant strains of HIV-1, HIV-2 and SHIV-AD8, an artificially made cross between HIV and simian immunodeficiency virus, an HIV relative found in monkeys. The protein was tested in cell cultures, mice with humanized immune systems and macaque monkeys given SHIV. This degree of protection far exceeds that of the strongest anti-HIV antibodies in the body's immune system.

For people, the protein could one day offer lasting protection against HIV infection by means of gene therapy, Farzan said. A designated gene would be carried into muscle cells by an innocuous virus. Then the gene, called eCD4-Ig, would be deposited into the muscle cells, where it would churn out the artificial protein into the bloodstream. If the protein encounters any HIV, it would bind to it, rendering the virus harmless.

In essence, the new study's authors said the approach acts as a vaccine against HIV.

Michael Farzan is a professor at the Florida campus of The Scripps Research Institute. / The Scripps Research Institute

The study was published Wednesday in the journal Nature. Farzan, in Scripps' campus in Jupiter, Florida, was the senior author. Matthew R. Gardner, also of Scripps Florida, was co-first author along with Lisa M. Kattenhorn of Harvard Medical School's New England Primate Research Center in Southborough, Mass. From Scripps' La Jolla headquarters, Dennis R. Burton, a noted expert on broadly neutralizing antibodies, also participated. More than 30 scientists in all took part in the study.

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Decoy protein stops all tested HIV strains

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