Navigation Links
Researchers identify possible key to slow progression toward AIDS
Date:9/19/2012

One of the big mysteries of AIDS is why some HIV-positive people take more than a decade to progress to full-blown AIDS, if they progress at all.

Although the average time between HIV infection and AIDS in the absence of antiretroviral treatment is about 10 years, some individuals succumb within two years, while so-called slow progressors can stay healthy for 20 years or longer.

Researchers already know that many slow progressors carry a gene called HLA-B*57 (B57), an immune gene variant that is found in less than 5 percent of the general population but in 40 to 85 percent of slow progressors. Yet even among those with the B57 gene, the speed of disease progression can vary considerably.

Now, a group of investigators from the Multi-Center AIDS Cohort Study (MACS), housed within the UCLA AIDS Institute, may have uncovered the key to this variation. It is a killer T-cell immune response that occurs early on in HIV infection and targets a section or epitope of the HIV protein called IW9.

The novel findings are featured on the cover of the October issue of the Journal of Virology.

"Since the hope for a vaccine is that it would elicit immune control, the thought has been that understanding how B57 protection works would yield helpful lessons and principles for vaccine design," said Catherine Brennan, an assistant research scientist in the department of medicine at the David Geffen School of Medicine at UCLA and the study's lead author. "There have been a lot of efforts to understand how the immune response to HIV in B57 carriers is superior to the response in non-B57 carriers, but it has been hard to nail anything down conclusively."

HLA-B genes are known to work by activating killer T cells that recognize unique sections of proteins, or epitopes, but it has been a mystery which section or sections of HIV protein HLA-B57 and the killer T cells work through.

Previous research had largely focused on the killer T-cell response after several years of infection. However, Beth D. Jamieson, a professor of medicine at the Geffen School of Medicine and the study's principal investigator, believes that the most critical responses are likely to occur early during infection, when the T cells are still strong and can reduce the number of places where HIV hides out in the human body.

Researchers have studied the immune response in the early months of infection, but since it is not easy to predict at early stages which people will ultimately become slow progressors, correlating early immune responses with long-term outcomes has been difficult.

"What made this kind of study possible for us is the Multicenter AIDS Cohort Study, which is an incredible longitudinal study," Brennan said.

The MACS has been freezing blood samples every six months since 1984 from thousands of men either at risk of HIV infection or already infected.

"The size and duration of the study, along with the careful documentation of participant health and stewardship of frozen samples, allowed us to recover blood samples taken shortly after HIV infection from 14 HLA-B57 carriers with known infection dates and known long-term outcomes," Brennan said. "This allowed us to correlate early immune responses with long-term outcomes."

It was important to the researchers to compare only the killer T-cell responses among those with the B57 gene variant, instead of comparing the responses of those with and without B57. Although B57 carriers have, on average, much better prognoses than non-carriers, there is tremendous variability among the population, and not all do well, Jamieson said.

"Since possession of the B57 variant is not sufficient, we wanted to determine what specific immune events in B57 carriers are associated with immune control of the virus," she said. "We found that those who targeted the IW9 epitope early in infection had significantly longer times until onset of AIDS than those who did not. The finding that targeting of IW9 seems to be important is novel, as this epitope had been overlooked in many earlier studies of B57 and HIV."

The researchers cautioned that the study was based on a small sample of only 14 individuals and that a wider pool of subjects is needed to replicate their findings. Also, their results point to a correlation with not causation of slower disease progression among B57 carriers who target the IW9 epitope soon after HIV infection.

"This work, although not powered by a large cohort and necessarily exploratory in nature, does suggest that the role of IW9 targeting in B57-mediated protection merits closer attention," the researchers conclude. "Understanding the detailed mechanisms by which B57 is associated with slow progression to disease will reveal underlying principles of immune control of HIV-1, which is critical for the development of rational vaccine-design strategies."


'/>"/>
Contact: Enrique Rivero
erivero@mednet.ucla.edu
310-794-2273
University of California - Los Angeles Health Sciences
Source:Eurekalert

Related medicine news :

1. UGA researchers boost efficacy of drugs by using nanoparticles to target powerhouse of cells
2. Researchers reveal underlying mechanism of powerful chemotherapy for prostate cancer treatment
3. Mayo Clinic researchers identify new enzyme to fight Alzheimers disease
4. UCI researchers find cause of chemotherapy resistance in melanoma
5. Majority of US Schools not ready for next pandemic, SLU researchers say
6. Researchers call for early diagnosis of flesh-eating infections
7. UMass Amherst sleep researchers study value of preschool naps
8. Moffitt cancer center researchers find novel predictor for MDS progression risk
9. HF/E researchers examine older adults willingness to accept help from robots
10. Local talent: Global impact public invited to meet world-class researchers at Queens
11. Researchers improve gene therapy technique for children with immune disorder
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... , ... June 25, 2016 , ... Austin residents seeking ... American College of Mohs Surgery and to Dr. Russell Peckham for medical and surgical ... effective treatment for skin cancer. The selective fellowship in Mohs Micrographic Surgery completed by ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... As a ... Magna Cum Laude and his M.D from the David Geffen School of Medicine at ... returned to Los Angeles to complete his fellowship in hematology/oncology at the UCLA-Olive View-Cedars ...
(Date:6/24/2016)... Los Angeles, CA (PRWEB) , ... June 24, 2016 , ... ... plastic surgery procedures that most people are unfamiliar with. The article goes on to ... known procedures, but also many of these less common operations such as calf and ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... Scientific Sessions in Dallas that it will receive two significant new grants to ... came as PHA marked its 25th anniversary by recognizing patients, medical professionals and ...
(Date:6/24/2016)... Rhinebeck, NY (PRWEB) , ... June 24, 2016 , ... Topical BioMedics, Inc, makers of ... of companies that call for a minimum wage raise to $12 an hour by 2020 ... wage. This will restore the lost value of the minimum wage, assure the wage floor ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... Mass. and SAN CLEMENTE, Calif. , ... California -based mobile pulmonary function testing company, is now able ... PFT devices developed by ndd Medical Technologies , Inc. ... testing done in hospital-based labs.  Thanks to ndd,s EasyOne PRO ® ... , can get any needed testing done in the comfort ...
(Date:6/24/2016)... , June 24, 2016  Arkis BioSciences, a ... invasive and more durable cerebrospinal fluid treatments, today ... The Series-A funding is led by Innova Memphis, ... and other private investors.  Arkis, new financing will ... and the market release of its in-licensed Endexo® ...
(Date:6/23/2016)... startling report released today, National Safety Council research shows ... plan to eliminate prescription opioid overdoses. Prescription Nation ... the worst drug crisis in recorded U.S. history, assigned a "Making ... , New Mexico , Tennessee ... states, three – Michigan , Missouri ...
Breaking Medicine Technology: