"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 HIV's 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 cell's 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 virus' 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
"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
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. The Howard Hughes Medical Institute also
provided support for this study.
Press releases, fact sheets and other NIAID-related materials are available
on the NIAID web site at http://www.niaid.nih.gov.