Navigation Links
Uncovering the Achilles' heel of the HIV-1 envelope
Date:1/11/2008

New structural details illustrate how a promising class of antibodies may block human immunodeficiency virus (HIV)-1 infection and reveal valuable clues for design of an effective HIV-1 vaccine. The findings, published by Cell Press in the January issue of Immunity, are particularly significant as antibody induction appears to be a key and necessary component of an effective HIV vaccine, evidenced by the recent failure of vaccines that stimulated only the T cell arm of the immune system to protect humans from contracting HIV-1.

Profound challenges have interfered with creation of a preventative vaccination to halt the global spread of HIV-1. For example, the HIV-1 envelope protein, the only target for neutralizing antibodies, is highly variable among isolates and masked by sugar molecules, allowing the virus to escape antibody attack. Not surprisingly, only a handful of broadly neutralizing antibodies (BNAbs) have been identified and they are rarely elicited during natural human infection, explains research leader Dr. Ellis L. Reinherz from the Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.

The BNAbs that have been identified are directed against a portion of HIV-1 called the membrane proximal ectodomain region (MPER). This region lies at the base of the viral envelope protein comprised of the gp120 protein plus the membrane anchoring gp41 subunits adjacent to the viral membrane. A major conundrum has been the basis for the lack of human antibody response against the MPER segment since it is accessible to antibody and is highly conserved, even among different HIV-1 viral isolates around the world.

The present study reveals that much of the MPER is actually embedded in the viral membrane. As such, this stealthy segment appears to divert the immune attack elsewhere, namely to the exposed variable elements of the viral envelope and immunodominant regions which do not confer useful neutralization. The researchers also discovered a hinge in the middle of the MPER permitting segmental flexibility, an important feature in facilitating fusion of the virus with the human host immune cells.

BNAbs such as the monoclonal 4E10 antibody target this hinge area and cause the MPER to undergo dynamic changes that reveal key pieces of itself critical for viral fusion that were buried deep in the membrane. As a result, the antibody is then able to achieve a tighter hold on the virus, restrict hinge mobility and impede the ability of the virus to fuse to the membrane of the host cell.

Importantly, the published structure of the lipid-embedded MPER also identifies those few residues poking out from the viral membrane. These may be ideal targets for vaccine design if properly configured in a synthetic lipid coat that conserves the native shape of the MPER and focuses production of antibodies against this Achilles' heel of the viral envelope.

While this research is still at an early experimental stage, it provides a plausible explanation as to why previous attempts, which neglected to preserve the native conformation of the MPER necessary for eliciting a broadly neutralizing antibody with 4E10-like specificity, were unsuccessful and offers a new approach to the design of antibody-eliciting vaccines to prevent HIV-1.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. UNCOVERING THE TRUTH - A Town Hall Meeting on Mental Health Parity
2. Ultrasound-guided injections help ease chronic Achilles tendon pain
3. Nations Largest Healthcare Alliance Adds Roche HIV-1 Test to Existing Contract
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... Orion, Clarkston, Michigan (PRWEB) , ... June 26, ... ... with respect to fertility once they have been diagnosed with endometriosis. These women ... intercourse but they also require a comprehensive approach that can help for preservation ...
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency ... named Dr. Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm facility. ... Director of our new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article published ... unfamiliar with. The article goes on to state that individuals are now more comfortable ... less common operations such as calf and cheek reduction. The Los Angeles area medical ...
(Date:6/24/2016)... ... 24, 2016 , ... Global law firm Greenberg Traurig, P.A. announced that 20 ... by their peers for this recognition are considered among the top 2 percent of ... honors as members of this year’s Legal Elite Hall of Fame: Miami Shareholders ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... today at the Clinical Decision Making in Emergency Medicine conference in Ponte Vedra ... authored journal articles published in Emergency Medicine Practice and Pediatric Emergency ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... DUBLIN , June 23, 2016 ... "Dialysis Devices Global Market - Forecast to 2022" report ... is the treatment method for the patients with kidney failure, ... and excess fluid from the patient,s blood and thus the ... sodium, potassium and chloride in balance. Increasing ...
(Date:6/23/2016)... , June 23, 2016 ... "Pharmaceutical Excipients Market by Type (Organic Chemical (Sugar, ... Formulation (Oral, Topical, Coating, Parenteral) - Global Forecast to ... The global pharmaceutical excipients market ... at a CAGR of 6.1% in the forecast period ...
(Date:6/23/2016)... 23, 2016 Roche (SIX: RO, ROG; OTCQX: ... its Elecsys BRAHMS PCT (procalcitonin) assay as a dedicated ... shock. With this clearance, Roche is the first IVD ... solution for sepsis risk assessment and management. ... and PCT levels in blood can aid clinicians in ...
Breaking Medicine Technology: