Proteins enable HIV to override cells defenses
Discovery of protein chain may lead to new drugs and treatments
Researchers at the Johns Hopkins Bloomberg School of Public Health have identified a complex series of proteins that enable HIV to bypass the natural defenses of human cells and replicate. The discovery of these proteins is the key for understanding how HIV overcomes host defenses and could potentially be new targets for HIV medications. A study detailing the finding is published in the October 16, 2003, online version of the journal Science.
As the researchers explained in their article, viruses like HIV contain a viral infectivity factor (Vif), which is essential for evading the human cells natural antiviral agent called APOBEC3G. To disable the antiviral agent, Vif interacts with a series of proteins to modify (polyubiquitination) and degrade APOBEC3G. Xiao-Fang Yu, MD, DSc, an associate professor with the Schools Department of Molecular Microbiology and Immunology, and his colleagues have identified these proteins as Cullin5, Elongins B and C and Rbx1. Together, they form a complex of proteins called ubiquitin E3 ligase (Cul5-SCF), which interacts with Vif and APOBEC3G.
"Weve discovered a new link in the chain that allows the HIV to overcome the cellular resistant factor and to infect human cells," said Dr. Yu. "By identifying the proteins involved in this process, we may be able to develop new drugs and therapies for preventing HIV infection."
Through a series of laboratory experiments, Dr. Yus team further found that disruption of the Cul5-SCF function makes HIV less infectious and less able of suppress APOBEC3G and its protective properties. HIV infectiousness was reduced 90 percent when Cul5 mutants were over expressed in combination with APOBEC3G.
Dr. Yu and his collaborators, Drs. Xianghui Yu, Yunkai Yu, Bindong Liu and Kun Luo, are working on further explaining the mechanism of Vif and Cul5 complex interaction and identifying strategies to block Vif function and consequently HIV infection.
"Induction of Ubiquitination and Degradation of APOBEC3G by HIV-1 Vif-Cul5-SCF" was written by Xianghui Yu, Yunkai Yu, Bindong Liu, Kun Luo, Wei Kong, Panyong Mao and Xiao-Fang Yu.
The study was funded by grants from National Center for Research Resources. Reagents were supplied by the AIDS Research Reagent Program, division of AIDS, NIAID, NIH.
Tim Parsons | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....