Navigation Links
Research suggests new cellular targets for HIV drug development
Date:5/27/2009

GAINESVILLE, Fla. Focusing HIV drug development on immune cells called macrophages instead of traditionally targeted T cells could bring us closer to eradicating the disease, according to new research from University of Florida and five other institutions.

In the largest study of its kind, researchers found that in diseased cells such as cancer cells that are also infected with HIV, almost all the virus was packed into macrophages, whose job is to "eat" invading disease agents.

What's more, up to half of those macrophages were hybrids, formed when pieces of genetic material from several parent HIV viruses combined to form new strains.

Such "recombination" is responsible for formation of mutants that easily elude immune system surveillance and escape from anti-HIV drugs.

"Macrophages are these little factories producing new hybrid particles of the virus, making the virus probably even more aggressive over time," said study co-author Marco Salemi, Ph.D., an assistant professor in the department of pathology, immunology and laboratory medicine at the UF College of Medicine. "If we want to eradicate HIV we need to find a way to actually target the virus specifically infecting the macrophages."

The work was published recently in the journal PLoS ONE.

At least 1.1 million people in the United States and 33 million in the world are living with HIV/AIDS, according to the Kaiser Family Foundation.

The researchers set out to see if HIV populations that infect abnormal tissues are different from those that infect normal ones, and whether particular strains are associated with certain types of illness.

They tackled the question using frozen post-autopsy tissue samples, pathology results and advanced computational techniques. They analyzed 780 HIV sequences from 53 normal and abnormal tissues from seven patients who had died between 1995 and 2003 from various AIDS-related conditions, including HIV-associated dementia, non-Hodgkin's lymphoma and generalized infections throughout the body. Four patients had been treated with highly active antiretroviral therapy, called HAART, at or near the time of death.

The researchers compared brain and lymphoma tissues, which had heavy concentrations of macrophages, with lymphoid tissues such as from the spleen and lymph nodes that had a mix of HIV-infected macrophages and T cells.

The analyses revealed great diversity in the HIV strains present, with different tissues having hybrid viruses made up of slightly different sets of genes. A high frequency of such recombinant viruses was also found in tissues generally associated with disease processes, such as the meninges, spleen and lymph nodes.

The researchers concluded that HIV-infected macrophages might be implicated in tumor-producing mechanisms.

The higher frequency of recombinant virus in diseased tissues likely is because macrophages multiply as a result of an inflammatory response, the researchers said.

"The study points to macrophages as a site of recombination in active disease," said neurobiologist Kenneth C. Williams, Ph.D., a Boston College associate professor and AIDS expert who was not involved in the study. "So people can say this is one spot where these viruses come from."

T cells the so-called conductors of the immune system orchestra, whose decline is the hallmark of HIV disease are an obvious target for HIV drug development because they die soon after infection, and are readily sampled from the blood and cultured. But although current drugs are effective at blocking infection of new cells and lowering viral loads to barely detectable levels, they never reduce the viral level in an infected person to zero.

"Where is it coming from?" said Michael S. McGrath, the University of California, San Francisco, professor who led the research team. "We believe it's coming from these macrophages."

Macrophages, like T cells, can be infected multiple times by HIV. But unlike T cells, when they get infected, they don't die within days, but live for several months, all the while being re-infected with multiple viruses of different genetic makeup. That situation is ripe for the emergence of hybrids.

"Most people who look at viral sequences assume that evolution of the virus is linear. In the real world that doesn't happen large parts of the virus are swapped in and out. This group has shown that in this model," Williams said. "It sort of overturns the old way of trying to match virus sequence with pathology."

McGrath's group is now developing macrophage-targeting drugs that, through a grant from the National Institute of Mental Health, should be in human clinical trials in a few years.

"This is one of the last frontiers killing off what we believe is a so far untouched reservoir," he said.


'/>"/>

Contact: Czerne M. Reid
czerne@ufl.edu
352-273-5814
University of Florida
Source:Eurekalert

Related medicine news :

1. Stanford researchers find culprit in aging muscles that heal poorly
2. Children of depressed moms do better when dad is involved, SLU researcher finds
3. UCLA researchers identify markers that may predict diabetes in still-healthy people
4. Mayo Clinic researchers discover new diagnostic test for detecting infection in prosthetic joints
5. New research shows how chronic stress worsens neurodegenerative disease course
6. New research explores newborn in-hospital weight loss
7. Research may unlock mystery of autisms origin in the brain
8. Bipolar disorder relapses halved by Melbourne researchers
9. HIVs impact in Zimbabwe explored in new research
10. U.S. Research Funding Continues to Flatten as U.S. Health Costs Climb - in August 31 Science
11. Cell that triggers symptoms in allergy attacks can also limit damage, Stanford researchers find
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/28/2017)... Calif. (PRWEB) , ... March 28, 2017 , ... ... its leading physicians, Paul Yost, will begin serving as new board chair for ... this month. Yost will serve the remainder of soon-to-be former chair Mark Refowitz’s ...
(Date:3/28/2017)... ... March 28, 2017 , ... ... of two biometric time and attendance tracking products: the new NCheck Cloud Bio ... Cloud Bio Attendance uses biometric face recognition to enable users to check in ...
(Date:3/28/2017)... (PRWEB) , ... March 28, 2017 , ... ... direct measurement of corrosive ions found in power plant water and steam. , ... such as turbines and boilers, leading to extensive maintenance and unplanned shutdowns. Monitoring ...
(Date:3/28/2017)... (PRWEB) , ... March 28, 2017 , ... The Executives, ... to raise money to for the Toys for Tots Literacy Campaign at their Semi-Annual ... in excess of $70 billion, the U.S. ranks at number 14 internationally in literacy. ...
(Date:3/28/2017)... ... March 28, 2017 , ... ... to achieve the “perfect smile.” The National Association of Dental Laboratories (NADL) is ... dentists should be aware of when utilizing dental laboratories and technicians that create ...
Breaking Medicine News(10 mins):
(Date:3/28/2017)... ALBANY, New York , March 28, 2017 /PRNewswire/ ... features a largely consolidated vendor landscape, with the top ... and Agilent Technologies accounting for a significant 49% of ... in a recent report. The vendor landscape is intensely ... large share in the overall market. These factors have ...
(Date:3/28/2017)... 2017 This morning,s research ... stocks: The Medicines Co. (NASDAQ: MDCO), Ironwood Pharmaceuticals ... and Supernus Pharmaceuticals Inc. (NASDAQ: SUPN ... space which is governed by the same governing ... the industry are wholesalers, retailers, pharmacies, and benefit ...
(Date:3/28/2017)... , March 28, 2017  Akcea Therapeutics, a subsidiary of ... the company,s board of directors: ... Mr. Gabrieli will serve as chairman of the board of ... chief commercial officer of Forest Laboratories. ... Partners. "We are excited to announce ...
Breaking Medicine Technology: