Navigation Links
Effective HIV control may depend on viral protein targeted by immune cells

An effective response of the immune system’s ‘killer?T cells against infection with HIV may depend on exactly which viral protein is targeted, according to an international group of researchers. A new study finds that HIV-infected individuals in whom virus-specific CD8 T cells are targeted against the Gag protein have lower viral levels than do those with CD8 responses directed against other viral proteins. The report from the Partners AIDS Research Center at Massachusetts General Hospital (PARC-MGH), the University of Oxford and University of KwaZulu-Natal in South Africa is receiving early online release in Nature Medicine.

"Understanding which immune responses are effective in control of HIV is of critical importance in vaccine development," says Philip Goulder, MD, PhD, of PARC-MGH and Oxford, the senior author of the study. "Previous approaches have focused on a ‘more is better?approach, seeking to generate responses against a broad range of viral proteins, but these results challenge that dogma."

While many strategies for developing a vaccine to control HIV focus on the activity of the CD8 T lymphocytes that recognize and destroy virus-infected CD4 T cells, the fact that even patients in the last stages of AIDS can have measurable CD8 responses indicates that those responses are not always effective. To investigate how variations in CD8 response alter the ability to control HIV, the research team enrolled almost 600 South African patients who had not yet been treated for their HIV infections.

The researchers comprehensively mapped the CD8 responses against all viral proteins and also investigated whether the versions of HLA Class I molecules involved in the immune system’s recognition of HIV protein fragments made a difference. When new viruses are produced within an infected cell, Class I molecules grab viral fragments and display them at the cell surface, thereby alerting CD8 cells that the cell has been infected and shoul d be destroyed. Earlier studies, including a 2004 Nature report from the same group, showed that the genetically determined version of an individual’s HLA Class I molecules could strongly influence immune control of HIV.

The current study found that only CD8 responses against the Gag protein were associated with significantly reduced viral levels and that individuals with responses against several different Gag fragments had even lower viral loads. In contrast, those with stronger responses against other HIV proteins ?including Env, a protein that is the focus of several vaccine studies ?had higher viral levels indicating poorer control of HIV.

In people receiving no antiretroviral treatment, the improved HIV control associated with Gag-specific CD8 response would probably translate into asymptomatic infection for more than a decade, compared with progression to AIDS within two to three years of infection in those with no Gag responses. The reason why patients?particular HLA Class I molecules are linked to different HIV disease outcomes now appears to be related to the number of Gag fragments displayed by different versions of the Class I molecule.

Mechanisms underlying the different effects of the protein-specific immune responses are unknown and require further investigation. The researchers suggest that responses against proteins like Env might be inherently less effective or might only be generated in response to elevated viral loads. Therefore, the findings of this study, which reflect chronic HIV infection, might not apply in situations in which vaccination generates an immune response before infection occurs.

"The possibility that there may be fundamental differences between the impact of Gag and non-Gag CD8 responses on the ability to control HIV has clear relevance to vaccine development," says Goulder, who is an associate professor of Medicine at Harvard Medical School.
'"/>

Source:Massachusetts General Hospital


Related biology news :

1. First-ever Compounds To Target Only Metastatic Cells Are Highly Effective Against Breast, Prostate, And Colon Cancers
2. Effective Cancer Treatments Follow The Clock
3. FDA Works To Speed The Advent Of New, More Effective Personalized Medicines
4. Fungus Effective Against Winged Termites
5. NCI Researchers Confirm the Effectiveness of Immunotherapy Approach to Treating Melanoma
6. Effective, safe anthrax vaccine can be grown in tobacco plants
7. Ancient olfaction protein is shared by many bugs, offering new pest control target
8. Gene variations explain drug dose required to control seizures
9. U-M scientists find genes that control growth of common skin cancer
10. Scientists discuss improved biopesticides for locust control in West Africa
11. Insight into natural cholesterol control suggests novel cholesterol-lowering therapy

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/10/2016)... BELL, Pa. , March 10, 2016   Unisys ... U.S. Customs and Border Protection (CBP) is testing its ... San Diego to help identify certain ... States . The test, designed to help determine the ... pedestrian environment, began in February and will run until May ...
(Date:3/9/2016)... Fla. , March 9, 2016  Crossmatch ... authentication and enrollment solutions, today announced the addition ... ® Altus multi-factor authentication platform. New ... InfoSec managers to step-up security where it,s needed ... Washington, DC . --> ...
(Date:3/3/2016)... Calif. , March 3, 2016  2016FLEX, ... launched this week highlighting advancements in flexible, hybrid ... a record setting attendance - have gathered for ... this fast-growing field of electronics. The Flex Conference ... focal point for companies, R&D organizations, and universities ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... ... May 25, 2016 , ... The Ankle ... plating options designed to address fractures of the distal tibia and fibula. This ... Acumed Ankle Plating System 3 is composed of seven plate families that span ...
(Date:5/25/2016)... ... May 25, 2016 , ... WEDI, the nation’s leading authority ... announced that Charles W. Stellar has been named by the WEDI Board of Directors ... 2016. As an executive leader with more than 35 years of experience in healthcare, ...
(Date:5/24/2016)... Israel , May 24, 2016   MedyMatch Technology ... physicians with artificial intelligence, real-time decision support tools in the ... present at the 2016 Israeli Advanced Technology Industries (IATI) BioMed ... Israel,s 15th National Life Sciences and ... at the David Intercontinental Hotel in Tel Aviv, ...
(Date:5/23/2016)... ... May 23, 2016 , ... PrecisionAg® Media ... in 2017 and Beyond. The paper outlines the key trends that are creating ... , “We’ve witnessed a lot of highs and lows as the precision agriculture ...
Breaking Biology Technology: