Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study may explain why HIV progresses faster in women than in men with same viral load

15.07.2009
Pathways related to elevated immune activation could lead to new treatment strategies

One of the continuing mysteries of the HIV/AIDS epidemic is why women usually develop lower viral levels than men following acute HIV-1 infection but progress faster to AIDS than men with similar viral loads.

Now a research team based at the Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard has found that a receptor molecule involved in the first-line recognition of HIV-1 responds to the virus differently in women, leading to subsequent differences in chronic T cell activation, a known predictor of disease progression. Their paper, which will be published in an upcoming issue of Nature Medicine, is receiving early online release.

"This study may help to account for reported gender differences in HIV-1 disease progression by demonstrating that women and men differ in the way their immune systems respond to the virus," says Marcus Altfeld, MD, PhD, of the Ragon Institute and the MGH Division of Infectious Disease, the study's senior author. "Focusing on immune activation separately from viral replication might give us new therapeutic approaches to limiting HIV-1-induced pathology."

It has become apparent in recent years that HIV-1-infected patients with a high level of immune activation progress to AIDS more rapidly. Why this happens is an area of intense investigation. To explore whether gender-based differences in immune activation were responsible for faster disease progression in women, the Ragon Institute team and their collaborators focused on plasmacytoid dendritic cells (pDCs), among the first cells of the immune system to respond to HIV-1 and other viral pathogens. Earlier studies indicated that pDCs recognize HIV-1 using a receptor called Toll-like receptor 7 (TLR7), leading to production of interferon-alpha and other important immune system molecules.

After initial in vitro experiments showed that a higher percentage of pDCs from uninfected women produced interferon-alpha in response to TLR7 stimulation by HIV-1 than did cells from uninfected men, the researchers examined whether women's hormone levels had any effect on pDC activation. Supporting previous evidence that progesterone may modulate pDC activity, the researchers found that pDCs from postmenopausal women produced levels of interferon-alpha in response to HIV-1 that were closer to levels observed in men. They also found that, in premenopausal women, higher progesterone levels correlated with increased activation of pDCs in response to HIV-1.

Since it is known that the activation of T cells predicts the progression of HIV-1 infection to AIDS, the research team conducted a series of in vitro experiments showing that the stimulation of pDCs in response to HIV-1 led to the subsequent activation of CD8+ T cells by means of interferon-alpha secretion. They then tested blood samples taken from a group of chronically HIV-1-infected women and men prior to treatment initiation and confirmed that women had higher levels of CD8+ T cell activation than did men with the same blood levels of HIV-1.

"Taken together, these results support a model in which the same amount of virus induces stronger pDC activation in women than in men. While stronger activation of the immune system might be beneficial in the early stages of infection, resulting in lower levels of HIV-1 replication, persistent viral replication and stronger chronic immune activation can lead to the faster progression to AIDS that has been seen in women," Altfeld explains.

He adds that the study's results raise a number of important new questions, including exactly how sex hormones modulate the TLR7-mediated response of pDCs to HIV-1 and whether anti-TLR agents may help reduce immune activation in chronic HIV-1 infection. His team is beginning preliminary laboratory studies of the ability of TLR antagonists to reduce HIV-1-induced activation of pDCs.

Altfeld is an associate professor of Medicine at Harvard Medical School and director of the Innate Immunity Program at the Ragon Institute of MGH, MIT and Harvard. Co-lead authors of the Nature Medicine paper are Angela Meier, MD, PhD, and J. Judy Chang, PhD, of the Ragon Institute. Additional co-authors are Harlyn Sidhu, Tom Fang Wen, Robert Lindsay, Suzane Bazner, Hendrik Streeck, MD, and Galit Alter, PhD, Ragon Institute; Gregory Robbins, MD, MGH Division of Infectious Diseases; Ronald Bosch, PhD, Ellen Chan, PhD, and Liliana Orellana, Harvard School of Public Health; Richard Pollard, MD, University of California at Davis Medical Center; Smita Kulkarni, PhD, Jeffrey Lifson, MD, and Mary Carrington, PhD, National Cancer Institute; and Donna Mildvan, MD, Beth Israel Medical Center, New York. The study was supported by grants from the National Institute of Allergy and Infectious Diseases, the Harvard Center for AIDS Research, the Bill & Melinda Gates Foundation, the Doris Duke Charitable Foundation, and the National Cancer Institute.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

Sue McGreevey | EurekAlert!
Further information:
http://www.mgh.harvard.edu

More articles from Studies and Analyses:

nachricht Smart Data Transformation – Surfing the Big Wave
02.12.2016 | Fraunhofer-Institut für Angewandte Informationstechnik FIT

nachricht Climate change could outpace EPA Lake Champlain protections
18.11.2016 | University of Vermont

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>