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!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy