Featured Research

from universities, journals, and other organizations

HIV-infected T cells help transport the virus throughout the body

Date:
August 1, 2012
Source:
Massachusetts General Hospital
Summary:
A new study has discovered one more way the human immunodeficiency virus (HIV) exploits the immune system. Not only does HIV infect and destroy CD4-positive helper T cells -- which normally direct and support the infection-fighting activities of other immune cells -- the virus also appears to use those cells to travel through the body and infect other CD4 T cells.

Mouse. A new study has discovered one more way the human immunodeficiency virus (HIV) exploits the immune system.
Credit: Vasiliy Koval / Fotolia

A new study has discovered one more way the human immunodeficiency virus (HIV) exploits the immune system. Not only does HIV infect and destroy CD4-positive helper T cells -- which normally direct and support the infection-fighting activities of other immune cells -- the virus also appears to use those cells to travel through the body and infect other CD4 T cells. The study from Massachusetts General Hospital (MGH) investigators, which will appear in the journal Nature and has received advance online release, is the first to visualize the behavior of HIV-infected human T cells within a lymph node of a live animal, using a recently developed "humanized" mouse model of HIV infection.

"We have found that HIV disseminates in the body of an infected individual by 'hitching a ride' on the T cells it infects," says Thorsten Mempel, MD, PhD, of the MGH Center for Immunology and Inflammatory Diseases, who led the study. "Infected T cells continue doing what they usually do, migrating within and between tissues such as lymph nodes, and in doing so they carry HIV to remote locations that free virus could not reach as easily. There are drugs that can manipulate the migration of T cells that potentially could be used to help control the spread of virus within a patient."

When HIV is introduced into blood or tissues, the virus binds to CD4 molecules on the surface of helper T cells, injecting its contents into cells and setting off a process that leads to the assembly and release of new virus particles. It has long been assumed that these free virus travel by diffusion through tissue fluids to encounter new cells that can be infected. But recent studies have suggested that HIV can also pass directly from cell to cell when structures called virological synapses form during long-lasting interactions between T cells. Since CD4 T cells usually migrate quickly and form only transient contacts with other cells, the current study was designed to examine whether HIV alters the migration of infected T cells, allowing the kind of persistent contact that facilitates the spread of infection.

The team's experiments used the humanized BLT mouse model, which has what is essentially a human immune system and is the only non-primate that can be infected with HIV. After first confirming that human T cells enter and normally migrate within the animals' lymph nodes -- known to be important sites of HIV replication -- the researchers injected the animals with HIV engineered to express green fluorescent protein (GFP), allowing them to track the movement of infected cells within living animals using a method called intravital microscopy. They first observed that, within two days, infected T cells continued to migrate and were uniformly distributed within lymph nodes but remained in nodes closest to the site of injection.

While the HIV-infected cells actively moved within lymph nodes, they did not move as quickly as comparable but uninfected T cells. In addition, 10 to 20 percent of the HIV-infected T cells formed abnormally long and thin extensions that appeared to trail behind moving cells, often exhibiting branches. The researchers hypothesized that the HIV envelope protein, which is expressed on the surface of infected T cells before they release new virus particles, might cause infected cells to form tethering contacts with uninfected cells, producing these extensions. A series of experiments verified that the elongated shape of some infected cells requires the presence of the envelope protein and that many of the elongated cells contained multiple nuclei, suggesting they had been formed by the fusion of several cells.

To test the role of T cell migration in HIV infection, the researchers injected another group of BLT mice with HIV and at the same time treated them with an agent that prevents T cells from leaving lymph nodes. Two months later, levels of HIV in the bloodstream and in lymph nodes distant from the site of injection were much lower than in untreated HIV-infected animals, supporting the importance of T cell migration to carry virus throughout the body. Treatment with the migration-suppressing agent, however, did not reduce viral levels in animals with already established HIV infection.

"While our observation of tethering interactions between infected and uninfected CD4-expressing cells suggest that HIV may be transmitted between T cells by direct contact, we will have to clearly show this in future studies and explore how important it is relative to the transmission by free virus," explains Mempel, an assistant professor of Medicine at Harvard Medical School. He adds that the availability of the BLT mouse was instrumental in their ability to carry out this study. "This approach provides a new vantage point to investigate previously unexplored aspects of HIV pathogenesis."


Story Source:

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


Journal Reference:

  1. Thomas T. Murooka, Maud Deruaz, Francesco Marangoni, Vladimir D. Vrbanac, Edward Seung, Ulrich H. von Andrian, Andrew M. Tager, Andrew D. Luster, Thorsten R. Mempel. HIV-infected T cells are migratory vehicles for viral dissemination. Nature, 2012; DOI: 10.1038/nature11398

Cite This Page:

Massachusetts General Hospital. "HIV-infected T cells help transport the virus throughout the body." ScienceDaily. ScienceDaily, 1 August 2012. <www.sciencedaily.com/releases/2012/08/120801132434.htm>.
Massachusetts General Hospital. (2012, August 1). HIV-infected T cells help transport the virus throughout the body. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2012/08/120801132434.htm
Massachusetts General Hospital. "HIV-infected T cells help transport the virus throughout the body." ScienceDaily. www.sciencedaily.com/releases/2012/08/120801132434.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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