Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

HIV infection requires B cells with special protein

14.07.2006
Study in PLoS Pathogens identifies new pathway that may aid in treating, preventing HIV

HIV infection of T cells requires activation of a molecule on the surface of B cells, a finding that reveals yet another pathway the virus uses in its insidious attack on the immune system, report University of Pittsburgh Graduate School of Public Health (GSPH) and School of Medicine researchers in PLoS Pathogens, an open-access journal published by the Public Library of Science. While preliminary, the research suggests a need for developing a class of antiviral drugs targeted against this molecule and offers an avenue that may prove critical for the prevention of HIV.

Nearly all approved HIV drug regimens and most of those being tested in clinical trials focus on T cells, where HIV replicates and thrives. HIV hijacks T cells by binding to a cell membrane molecule called CD4 and to either or both of two other receptors, from which the two strains of HIV, X4 and C5, take their names. Once anchored on the membrane, it's able to slither inside and take command of the cell. The new research identifies an important first step in a new pathway involving B cells that express a protein called DC-SIGN. While these cells themselves do not become infected, they play a pivotal role as an accomplice in HIV's takeover of T cells.

"We have new insight into how the virus does its damage. The pathway is surprisingly simple, yet it has important implications for future studies and drug development efforts that focus on reservoirs of HIV in cells other than T cells," said Charles R. Rinaldo, Jr., Ph.D., professor and chairman of the department of infectious diseases and microbiology at Pitt's GSPH and the study's senior author.

The researchers report evidence of DC-SIGN in subsets of B cells from both healthy subjects and HIV infected individuals. Laboratory studies of these cells indicate DC-SIGN is a point of entry for HIV and necessary for T cell infection.

B cells were isolated from blood samples obtained in 33 healthy subjects and 20 adult patients with HIV from the Multicenter AIDS Cohort Study (MACS), 10 of whom had suppressed virus due to antiretroviral therapy (ART) and 10 who had never undergone ART. Researchers found about 8 percent of these cells expressed DC-SIGN. The researchers also confirmed their presence in tissue by examining samples from five non-HIV tonsillectomy patients. In tonsils, a lymphoid organ where both T cells and B cells congregate and engage in cross talk, 26 percent of the B cells expressed DC-SIGN.

In one set of studies involving cells from the healthy subjects, the team activated DC-SIGN using two molecules that T cells typically engage in their communication with B cells. Once activated, the DC-SIGN B cells were placed in a culture with T cells and a small amount of virus. Within 24 hours, HIV had invaded the T cells while sparing the B cells. When researchers repeated the experiment without B cells, the HIV had little effect on the T cells alone. Pretreating the B cells with a molecule that blocks DC-SIGN activation before culturing them with both T cells and HIV was a deterrent against T cell infection as well, further proof that to invade T cells, HIV requires DC-SIGN expressed on B cells.

DC-SIGN was first identified as a dendritic cell-specific binding site for HIV, but with this study, Dr. Rinaldo and colleagues prove that B cells expressing DC-SIGN also are used by HIV to facilitate infection of T cells.

"As has been observed in DC-SIGN dendritic cells, we suspect the B cells internalize the virus and that the DC-SIGN serves as sort of a bridge HIV uses to reach the surface of T cells," noted Giovanna Rappocciolo, Ph.D., associate professor of infectious diseases and microbiology at GSPH and the study's first author.

Lisa Rossi | EurekAlert!
Further information:
http://www.upmc.edu/

More articles from Life Sciences:

nachricht Algae: The final frontier
22.06.2017 | Carnegie Institution for Science

nachricht Flipping the switch to stop tumor development
22.06.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Hubble captures massive dead disk galaxy that challenges theories of galaxy evolution

22.06.2017 | Physics and Astronomy

New femto-camera with quadrillion fractions of a second resolution

22.06.2017 | Physics and Astronomy

Rice U. chemists create 3-D printed graphene foam

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>