Navigation Links
NIAID scientists identify new cellular receptor for HIV
Date:2/9/2008

A cellular protein that helps guide immune cells to the gut has been newly identified as a target of HIV when the virus begins its assault on the body's immune system, according to researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

The identification of this new receptor opens up new avenues of investigation that may help further elucidate the complex mechanisms of the pathogenesis of HIV infection, says NIAID Director Anthony S. Fauci, M.D., chief of the Institutes Laboratory of Immunoregulation (LIR) and senior author of the new study.

Several other immune cell receptors bind to HIV. Most important among these, the CD4 molecule, identified as an HIV receptor in 1984, functions as the principal receptor for HIV. The CCR5 and CXCR4 molecules, discovered in 1996, serve as co-receptors that HIV uses to enter its target cells. In the new study, which appears online Feb. 10, 2008 in Nature Immunology, NIAID scientists identify a cell adhesion molecule known as integrin alpha 4 beta 7 as another potentially important receptor for HIV.

Early in the course of HIV infection, the virus rapidly invades and replicates in gut-associated lymphoid tissue (GALT), the immune cells of the gut. Once seeded with HIV, the gut is rapidly depleted of CD4+ T cells, the main target of HIV, triggering the process that ultimately leads to AIDS.

In the very early days of infection, it is in the GALT where most of the damage caused by HIV occurs, says Elena Martinelli, Ph.D., a lead author of the paper and a fellow in Dr. Faucis laboratory. The gut is where the virus really takes hold. We found that integrin alpha 4 beta 7, whose natural function is to direct T cells to the GALT, is also a receptor for HIV. It is very unlikely that this is a coincidence.

Dr. Martinelli, along with Claudia Cicala, Ph.D., James Arthos, Ph.D., and their colleagues found that the gp120 protein, part of the HIV envelope, binds to integrin alpha 4 beta 7 on CD4+ T cells, which promotes the formation of a stable junction, or synapse, between neighboring cells.

A synapse is a junction that allows two cells to adhere in a stable way, says Dr. Arthos. Many viruses have found a way to trick cells into forming these stable junctions. Now it appears that HIV can also trigger synapse formation.

Specifically, a short piece of the HIV gp120 protein in a region known as the V2 loop recognizes the alpha 4 chain of the integrin molecule on host cells. This stretch of the V2 loop is similar to part of the naturally occurring molecules that bind integrin alpha 4 beta 7. Thus, it appears that HIV is mimicking the natural molecular partners, or ligands, that normally bind to the receptor. The authors note, however, that some HIV isolates react more strongly to integrin alpha 4 beta 7 than others.

The ability of a particular virus to bind to integrin alpha 4 beta 7 may determine whether it will have a major impact in targeting the gut lymphoid tissue, says Dr. Fauci. This finding could be a significant determinant in the pathogenic mechanisms that lead to AIDS.

As part of the natural homing process, integrin alpha 4 beta 7 binds to its natural ligands and activates a protein known as LFA-1. According to Dr. Arthos, HIV can co-opt this process by mimicking the cells alpha 4 beta 7 receptor natural ligands. When HIV gp120 protein binds to the alpha 4 beta 7 receptor it facilitates the formation of a synapse. Thus, HIV tricks an infected cell into binding to an uninfected cell, enabling HIV to readily gain access to the uninfected cell.

While this study provides important new information concerning the various mechanisms by which HIV debilitates the human immune system, it also raises new questions and challenges that our laboratory and others will pursue, notes Dr. Cicala.


'/>"/>

Contact: NIAID Office of Communications
niaidnews@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
Source:Eurekalert

Related medicine news :

1. NIAID strengthens and expands Vaccine and Treatment Evaluation Units
2. NIAID funds $51M contract to create comprehensive model of immune responses
3. ECNP launches research grant for young scientists
4. Scientists confirm new virus responsible for deaths of transplant recipients in Australia
5. Bonn scientists simulate dinosaur digestion in the lab
6. Scripps scientists peg wind as the force behind fish booms and busts
7. Chemical signature of manic depression discovered by scientists
8. Bug guts map brings scientists closer to understanding different bugs role in the body
9. Scripps scientists find calcium channel blockers help normalize lysosomal storage disease cells
10. Global Consensus on Mercury: Scientists Defend Science Journalists
11. DuPont Hosts Meeting of Leading Plant Scientists to Improve World Agricultural Productivity
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... Talented host, actor ... on sciatica in a new episode of "Success Files," which is an award-winning ... innovation and investigates each subject in-depth with passion and integrity. , Sciatica occurs ...
(Date:10/13/2017)... ... October 13, 2017 , ... “America On The Brink”: the ... “America On The Brink” is the creation of published author, William Nowers. Captain ... As a WWII veteran, he spent thirty years in the Navy. Following his ...
(Date:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and ... plans to open a flagship location in Covington, LA at 401 N. U.S. Highway ... store next to Office Depot in the Holiday Square shopping center. Its location allows ...
(Date:10/12/2017)... ... 2017 , ... The American College of Medical Informatics (ACMI) will present the ... Opening Session of AMIA’s Annual Symposium in Washington, D.C. AMIA’s Annual Symposium ... a pioneer in the field of medical informatics, this prestigious award is presented to ...
(Date:10/12/2017)... ... October 12, 2017 , ... Dr. Parsa Mohebi, the Los ... article to the newly revamped Cosmetic Town journal section, featuring articles ... procedure known as Follicular Unit Extraction (FUE). , Dr. Mohebi says ...
Breaking Medicine News(10 mins):
(Date:10/4/2017)... South Korea , Oct. 4, 2017  South ... its next-generation CPR training aide "cprCUBE" on Kickstarter. The ... chest compression during cardiac arrests with better efficiency compared ... It also offers real-time feedback on efficacy of the ... The crowdfunding campaign has a goal to raise $5,000. ...
(Date:10/2/2017)... ORLANDO, Fla. , Oct. 2, 2017  AllianceRx ... services company formed by Walgreens and pharmacy benefit manager ... of its new brand, which included the unveiling of ... Fla. , as well as at a few ... introduces the new brand to patients, some of whom ...
(Date:9/27/2017)... -- Commended for their devotion to personalized service, SMP Pharmacy Solutions ... in the South Florida Business Journal,s 50 Fastest-Growing Companies, and ... the national specialty pharmacy has found its niche.  To that ... be honored by SFBJ as the 2017 Power Leader in ... receive his award in October, Bardisa said of the three ...
Breaking Medicine Technology: