New Drugs Could Target the HIV Release Mechanism

AIDS researchers have identified the HIV protein that is used by the virus to overcome the host cell's defensive mechanism that would normally prevent release of virus particles from the infected cell. Inhibition of this protein, Vpu in HIV-1 or Env in HIV-2, could form the basis for new therapeutic strategies against HIV.

Investigators at Emory University (Atlanta, GA, USA) reported in the May 25, 2008, online edition of the journal Nature Medicine that the human cellular protein calcium-modulating cyclophilin ligand (CAML) normally prevented HIV release. They showed that African green monkey cells, which do not contain CAML, freely released HIV.

The virus, however, has developed a molecular mechanism to counter the action of CAML; and the HIV-1 viral protein Vpu or the similar HIV-2 Env protein is the culprit. In experiments where Vpu was depleted, HIV particles did not detach from the plasma membrane of the host human cell and instead accumulated at the cell surface. The addition of the gene for production of CAML to African green monkey cells conferred a strong restriction of virus release that was reversed by Vpu and Env. Depletion of CAML in human cells eliminated the need for Vpu in enhancing HIV-1 release.

"This research is important because it identifies CAML as an innate defense mechanism against HIV,” explained senior author Dr. Paul Spearman, professor of pediatrics at Emory University. "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.”


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