AEGiS-NIAID: Molecular Traffic Signal Could Be New HIV Drug Target

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Molecular Traffic Signal Could Be New HIV Drug Target

NIAID, National Institutes of Health - Wednesday, Dec. 8, 1999
John Bowersox, Laurie K. Doepel - (301) 402-1663

A single HIV protein acts as a molecular traffic signal to regulate crucial steps in the virus' life cycle, a new study has found. The discovery of these previously unrecognized stop-and-go functions provides new targets for creating molecular gridlock and halting virus growth. A research team led by Michael R. Green, M.D., Ph.D., and Mario Stevenson, Ph.D., of the University of Massachusetts Medical Center in Worcester, reports the findings in the Dec. 9, 1999 issue of Nature.

"This study helps fill in a missing piece of the HIV reproduction process," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), which funded the study. "The findings suggest we may be able to devise therapies that subvert the order and timing of cellular events necessary for HIV replication."

By systematically analyzing the properties of normal and mutant forms of HIV, Drs. Green, Stevenson and their colleagues found that a molecule known as HIV matrix protein, an important building block within HIVÆs core, controls two opposing functions. Each function comes into play during a different stage in the HIV infection cycle.

For HIV to reproduce inside human cells, it must first invade the nucleus and commandeer the cellÆs genetic machinery. "Early after HIV infection, matrix protein helps import HIV genetic material into the nucleus of the infected cell," says Dr. Green. Once inside the nucleus, HIV co-opts the genetic machinery to churn out copies of the virusÆ genetic material, called RNA. That viral RNA then forms the genetic blueprints from which new HIV proteins are constructed.

Later in the infection cycle, the matrix protein reverses the flow of traffic and directs new HIV proteins away from the nucleus and into the surrounding cell cytoplasm where new viruses are assembled and packaged.

"How matrix protein suddenly reverses course has been a mystery," says Dr. Green. "Our study shows that the nuclear export signal kicks in late after infection."

"These data confirm what other studies have suggested - that matrix protein helps localize HIV genetic material to the cell nucleus so that integration and transcription can take place," notes Nava Sarver, Ph.D., chief of the targeted interventions branch in NIAID's Division of AIDS. "The evidence that the matrix protein also has a nuclear export activity required for viral replication is exciting new information.

"The opposing functions of the HIV matrix protein represent two new discrete targets for anti-HIV drugs," adds Dr. Sarver. "Drugs designed to block either the import or export signals can undermine the carefully orchestrated course of events during HIV replication, and could shut down the growth of the virus."

Note: The Howard Hughes Medical Institute also provided support for this study.

###

Reference: S Dupont, N Sharova, C DeHoratius, C-MA Virbasius, X Zhu, AG Bukrinskaya, M Stevenson and MR Green. A novel nuclear export activity in HIV-1 matrix protein required for viral replication. Nature 402:681-85 (1999).

NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov. For more information on HIV/AIDS, please visit the NIAID AIDS publications page.
991208
NI991201

Published 1999 - National Institute of Allergy and Infectious Diseases . All material contained in this report is in the public domain and may be used and reprinted without special permission; citation to source, however, is appreciated.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Broadway Cares/Equity Fights AIDS, the Elton John AIDS Foundation, National Library of Medicine, and donations from users like you.

Always watch for outdated information. This article first appeared in 1999. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1999. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .