Featured Research

from universities, journals, and other organizations

Researchers Discover New Way To Block HIV Transmission By Removing Cholesterol From Cell Membrane: Hopkins Study Finds HIV Requires Cholesterol To Infect

Date:
July 25, 2001
Source:
Johns Hopkins Medical Institutions
Summary:
Cholesterol is instrumental in HIV's ability to infiltrate cells, and removing this fatty material from a cell's membrane blocks infection, according to a Johns Hopkins study reported in the July 20th issue of AIDS Research and Human Retroviruses. The discovery may provide new opportunities to stop HIV transmission.

Cholesterol is instrumental in HIV's ability to infiltrate cells, and removing this fatty material from a cell's membrane blocks infection, according to a Johns Hopkins study reported in the July 20th issue of AIDS Research and Human Retroviruses. The discovery may provide new opportunities to stop HIV transmission.

"With a vaccine not immediately on the horizon, microbicides that can remove cholesterol from cell membranes, rendering HIV non-infectious, may play an important part in controlling the AIDS pandemic," says James Hildreth, M.D., Ph.D., associate professor of pharmacology and molecular science at Johns Hopkins and principal investigator of the study.

Researchers found that a starchy substance that drains cholesterol from a cell's membrane can completely block HIV transmission. Using microbicides that contain this cholesterol-depletor during sex should be able to reduce or stop HIV transmission, according to the study.

Researchers have long known that HIV steals many proteins from a cell membrane when it exits the cell. The theft of adhesion proteins, for example, allows the virus to bind to many cell types, increasing its infectious nature. Scientists wondered, however, why a particular protein called CD45 was plentiful in cell membranes but ignored in HIV's robbery efforts. Looking closely at the issue, Hildreth observed that lipid rafts, subregions of a cell's membrane enriched with certain lipids and cholesterol, do not contain this protein.

"We thought that because HIV leaves behind CD45, and because CD45 doesn't exist in the lipid rafts, then maybe HIV emerges from the lipid rafts when it exits a cell," says Hildreth. Studies showed that indeed this was true, and in the current report, researchers focused on solving the next question.

"We wondered why lipid rafts might be important for HIV biology, and our attention focused on cholesterol in the rafts because it's important in a number of biological functions, including fusion," says Hildreth. "We also knew that certain other viruses require cholesterol for infection."

To test their hypothesis, the scientists manipulated cholesterol levels by using cyclodextrins, chains of sugar polymers that form circles or rings. The insides of these rings provide a hydrophobic environment, one that is appealing to molecules that hate water. Since molecules such as cholesterol are hydrophobic, they like to sit inside the rings. The researchers removed cholesterol from several primary cell lines by treating them with cyclodextrins, allowing the rings to absorb the fat-like material. They then exposed these cells to virus particles and cells infected with HIV.

To their surprise, the scientists discovered that cholesterol was not only crucial for the virus' exit but also for its entrance into a cell. When exposed to the virus, treated cells resisted HIV infection.

Upon further inspection, the researchers discovered that removing cholesterol reduces the number of so-called chemokine receptors, HIV co-receptors that the virus must latch onto to gain entry into a cell. Hildreth believes that in the absence of cholesterol, a rigid substance, these receptors lose their shape, become unstable and are destroyed. Cholesterol's stiffening quality is actually responsible for the name "lipid raft." This fatty material stiffens the lipid soup, and subregions then appear as little boats or rafts floating in the more liquid components of the membrane.

The researchers have tested the cyclodextrins with both HIV-1 and SIV, a close cousin of HIV that affects monkeys, and thus believe cyclodextrins will similarly affect all viral strains. "Cholesterol plays a crucial role in the biology of the virus. The finding that cyclodextrins can stop infection is allowing us to develop an entirely new strategy for blocking sexual transmission of HIV using microbicides," says Hildreth. "Cyclodextrins have been used in humans for many years as a carrier for hydrophobic drugs so the molecule already has a proven safety profile. And remarkably, it's non-toxic to cells."

In the future, researchers hope that creams that contain the cholesterol-depleting sugar rings will be used to coat the inside of the vagina or rectum to reduce infection. Topical creams could be applied immediately before intercourse or cervical rings containing the microbicides could provide a slow release of the chemical over many weeks.

Other authors of the study include Zhaohao Liao, Lisa Cimakasky, Richard Hampton and Dzung Nguyen from Johns Hopkins. The study was funded by grants from the Public Health Service, an institutional grant from the Johns Hopkins University School of Medicine, and the Johns Hopkins Fund for Medical Discovery.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "Researchers Discover New Way To Block HIV Transmission By Removing Cholesterol From Cell Membrane: Hopkins Study Finds HIV Requires Cholesterol To Infect." ScienceDaily. ScienceDaily, 25 July 2001. <www.sciencedaily.com/releases/2001/07/010725081921.htm>.
Johns Hopkins Medical Institutions. (2001, July 25). Researchers Discover New Way To Block HIV Transmission By Removing Cholesterol From Cell Membrane: Hopkins Study Finds HIV Requires Cholesterol To Infect. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2001/07/010725081921.htm
Johns Hopkins Medical Institutions. "Researchers Discover New Way To Block HIV Transmission By Removing Cholesterol From Cell Membrane: Hopkins Study Finds HIV Requires Cholesterol To Infect." ScienceDaily. www.sciencedaily.com/releases/2001/07/010725081921.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Snack Attack: Study Says Action Movies Make You Snack More

Snack Attack: Study Says Action Movies Make You Snack More

Newsy (Sep. 2, 2014) You're more likely to gain weight while watching action flicks than you are watching other types of programming, says a new study published in JAMA. Video provided by Newsy
Powered by NewsLook.com
U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. 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