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:6/26/2016)... , ... June 26, 2016 , ... PawPaws brand ... new product that was developed to enhance the health of felines. The formula is ... The two main herbs in the PawPaws Cat Kidney Support Supplement Soft ...
(Date:6/25/2016)... Austin, TX (PRWEB) , ... June 25, 2016 , ... ... Fellow of the American College of Mohs Surgery and to Dr. Russell Peckham for ... popular and highly effective treatment for skin cancer. The selective fellowship in Mohs Micrographic ...
(Date:6/25/2016)... ... June 25, 2016 , ... As a lifelong Southern Californian, Dr. ... his M.D from the David Geffen School of Medicine at UCLA. He trained in ... to complete his fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he ...
(Date:6/24/2016)... ... 2016 , ... A recent article published June 14 on E ... goes on to state that individuals are now more comfortable seeking to undergo not ... as calf and cheek reduction. The Los Angeles area medical group, Beverly Hills Physicians ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... Sessions in Dallas that it will receive two significant new grants to support ... as PHA marked its 25th anniversary by recognizing patients, medical professionals and scientists ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... Va. , June 24, 2016 The ... set of recommendations that would allow biopharmaceutical ... (HCEI) with entities that make formulary and coverage decisions, ... the "value" of new medicines. The recommendations ... does not appear on the drug label, a prohibition ...
(Date:6/24/2016)... , June 24, 2016  American Respiratory Labs (ARL), a ... now able to perform sophisticated lung assessments in patients, homes, thanks ... Inc. Patients are no longer limited to having ... PRO ® , ARL patients like Jeanne R. of ... the comfort of her own home. ...
(Date:6/24/2016)... -- According to a new market research ... Safety Pen Needles), Needle Length (4mm, 5mm, 6mm, 8mm, ... Purchase (Retail, Non-Retail) - Trends & Global Forecasts to ... for the forecast period of 2016 to 2021. This ... 2021 from USD 1.65 Billion in 2016, growing at ...
Breaking Medicine Technology: