Featured Research

from universities, journals, and other organizations

Uncovering The Achilles' Heel Of The HIV-1 Envelope

Date:
January 15, 2008
Source:
Cell Press
Summary:
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.

Rendering of HIV virus.
Credit: iStockphoto/Sebastian Kaulitzki

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 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.

The findings are published by Cell Press in the January issue of Immunity.

The researchers include Zhen-Yu J. Sun, Harvard Medical School, Boston, MA, USA; Kyoung Joon Oh, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Mikyung Kim, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Jessica Yu, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Vladimir Brusic, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Likai Song, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Zhisong Qiao, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Jia-huai Wang, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Gerhard Wagner, Harvard Medical School, Boston, MA, USA; and Ellis L. Reinherz, Harvard Medical School, Boston, MA, USA, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Uncovering The Achilles' Heel Of The HIV-1 Envelope." ScienceDaily. ScienceDaily, 15 January 2008. <www.sciencedaily.com/releases/2008/01/080111105342.htm>.
Cell Press. (2008, January 15). Uncovering The Achilles' Heel Of The HIV-1 Envelope. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2008/01/080111105342.htm
Cell Press. "Uncovering The Achilles' Heel Of The HIV-1 Envelope." ScienceDaily. www.sciencedaily.com/releases/2008/01/080111105342.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Newsy (July 23, 2014) An 8-year-old boy helped his younger brother, who has a rare genetic condition that's confined him to a wheelchair, finish a triathlon. Video provided by Newsy
Powered by NewsLook.com
Thousands Who Can't Afford Medical Care Flock to Free US Clinic

Thousands Who Can't Afford Medical Care Flock to Free US Clinic

AFP (July 23, 2014) America may be the world’s richest country, but in terms of healthcare, the World Health Organisation ranks it 37th. Thousands turned out for a free clinic run by "Remote Area Medical" with a visit from the Governor of Virginia. Duration: 2:40 Video provided by AFP
Powered by NewsLook.com
Stone Fruit Listeria Scare Causes Sweeping Recall

Stone Fruit Listeria Scare Causes Sweeping Recall

Newsy (July 22, 2014) The Wawona Packing Company has issued a voluntary recall on the stone fruit it distributes due to a possible Listeria outbreak. Video provided by Newsy
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins