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Protein That Provides Innate Defense Against HIV Could Lead To New Treatments

Date:
May 26, 2008
Source:
Emory University
Summary:
The HIV-1 protein Vpu is necessary for the HIV-1 virus to be released from human cells. Scientists have identified CAML as a human cellular protein that blocks the release of HIV-1 viral particles from the membrane of infected cells. The Vpu protein is able to counteract the effects of CAML and allow the release of HIV-1 particles. Understanding how CAML provides an innate defense against HIV and how Vpu counteracts this defense should help scientists develop new treatments.

By identifying a protein that restricts the release of HIV-1 virus from human cells, scientists believe they may be closer to identifying new approaches to treatment.

Scientists have known that most human cells contain a factor that regulates the release of virus particles, but until now they have been uncertain about the factor's identity. Now a research team from Emory University School of Medicine, Vanderbilt University School of Medicine, and Mayo Medical School has identified CAML (calcium-modulating cyclophilin ligand) as the cellular protein that inhibits the release of HIV particles.

CAML works by inhibiting a very late step in the virus lifecycle, leading to the retention of HIV particles on the membrane of the cell. The virus has developed a means of counteracting CAML, through the action of the viral Vpu protein. When Vpu is absent, HIV particles don't detach from the plasma membrane and instead accumulate by a protein tether at the cell surface.

When the research team depleted CAML in human cells in the laboratory, they found that Vpu was no longer required for the efficient exit of HIV-1 particles from the cell. When they expressed CAML in cell types that normally allow particles to exit freely, the particles remained attached to the cell surface.

"This research is important because it identifies CAML as an innate defense mechanism against HIV," says senior author Paul Spearman, professor of pediatrics (infectious diseases) at Emory University School of Medicine. "We are continuing to work on the mechanism that Vpu uses to counteract CAML and on defining exactly how CAML leads to virus particle retention on the infected cell membrane. We hope this will lead us to new treatments."

The research was funded by the National Institutes of Health.


Story Source:

The above story is based on materials provided by Emory University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Varthakavi et al. Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu. Nature Medicine, 2008; 14 (6): 641 DOI: 10.1038/nm1778

Cite This Page:

Emory University. "Protein That Provides Innate Defense Against HIV Could Lead To New Treatments." ScienceDaily. ScienceDaily, 26 May 2008. <www.sciencedaily.com/releases/2008/05/080525132341.htm>.
Emory University. (2008, May 26). Protein That Provides Innate Defense Against HIV Could Lead To New Treatments. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2008/05/080525132341.htm
Emory University. "Protein That Provides Innate Defense Against HIV Could Lead To New Treatments." ScienceDaily. www.sciencedaily.com/releases/2008/05/080525132341.htm (accessed October 22, 2014).

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