How HIV cripples immune cells

Sep 16, 2009
This is the actin cytoskeleton of human T-lymphocytes (red) in the presence of the stimulus CCL-19. An HIV-1 infection (HIV-1 protein CA in green) leads to the loss of actin reorganization and therefore of cell motility. Credit: Source: Hygiene Institute, Heidelberg University Hospital.

In order to be able to ward off disease pathogens, immune cells must be mobile and be able to establish contact with each other. The working group around Professor Dr. Oliver Fackler in the Virology Department of the Hygiene Institute of the Heidelberg University Hospital has discovered a mechanism in an animal model revealing how HIV, the AIDS pathogen, cripples immune cells: Cell mobility is inhibited by the HIV Nef protein. The study was published in the highly respected journal "Cell Host & Microbe". This discovery may have pointed the way towards a new treatment approach.

Over 30 million persons worldwide are infected with . Typically, after the initial infection accompanied by acute symptoms, there is a latency period of several years before the acquired immune deficiency syndrome (AIDS) manifests. The human immunodeficiency virus (HIV) has developed numerous strategies for eluding the body's defenses and the medications administered. The prerequisite for efficient reproduction of the virus in the patient's body is the virus's own Nef protein. Without Nef, the development of AIDS is significantly slowed or even stopped completely. The underlying mechanism of this observation was a complete mystery up to now, however.

HIV modifies the cell structure system of the host cells

Viruses alter the support structures of affected cells, enabling them to enter the cells more easily. The cell structure element actin, which also gives muscles their mobility, aids in the motility of immune cells. This is necessary for immune cells to be able to establish contact with each other and combat the virus. After each movement, actin must be returned to its original state in order to be available once again. HIV especially attacks immune cells of the T-helper type. These cells support not only direct "defense against the enemy", but are also necessary for building sufficient antibodies against the invader. For this, they must rely on their mobility.

Short-circuiting of two different signal paths in the cell by Nef

The researchers examined the movement of cells in living zebra fish embryos and were able to show that cell mobility is inhibited by the HIV Nef protein. As they continued their experiments on cell cultures, they were able to explain the underlying mechanism: Nef causes an enzyme that normally has nothing to do with cell mobility to deactivate a regulator for actin regeneration. Nef therefore causes a short-circuit of two cellular mechanisms, thus inhibiting the reorganization of the element actin and the cell's ability to move. Thus, the affected can no longer fulfill their function.

"We speculate that the negative effect of Nef on the mobility of T-helper cells has far reaching consequences for the efficient formation of antibodies by B-lymphocytes in the patient. The mechanism we have described could be involved in the increasingly observed malfunction of B-lymphocytes in patients", explains Professor Fackler. Up to now, Nef has not been a target of antiviral therapy. Since one of the first molecular mechanisms has now been decoded, however, and the importance of Nef for the disease has become clearer, this could change in the future.

More information: HIV-1 Nef Interferes with Host Cell Motility by Deregulation of Cofilin. Bettina Stolp, Michal Reichman-Fried, Libin Abraham, Xiaoyu Pan, Simone I. Giese, Sebastian Hannemann, Polyxeni Goulimari, Erez Raz, Robert Grosse, Oliver T. Fackler. Cell Host & Microbe, 2009 Aug 20;6(2):174-86. DOI:10.1016/j.chom.2009.06.004

Source: University Hospital Heidelberg (news : web)

Explore further: Study models ways to cut Mexico's HIV rates

add to favorites email to friend print save as pdf

Related Stories

How HIV hides itself

Apr 01, 2008

Researchers have discovered how Human Immunodeficiency Virus (HIV), which causes AIDS, can hide itself in our cells and dodge the attention of our normal defences, scientists heard today at the Society for General Microbiology’s ...

New target for HIV/AIDS drugs and vaccine discovered

Jul 26, 2007

Researchers from Rome, Italy, describe a finding in the August 2007 print issue of The FASEB Journal that could lead to new drugs to fight the HIV/AIDS virus, as well as new vaccines to prevent infection.

Mutant host cell protein sequesters critical HIV-1 element

Jan 15, 2009

Scientists have identified a new way to inhibit a molecule that is critical for HIV pathogenesis. The research, published by Cell Press in the January 16th issue of the journal Molecular Cell, presents a target for develo ...

Scientists find another key to HIV success

Mar 22, 2006

Weill Cornell Medical College scientists say they've determined a protein produced by HIV infected cells prevents immune B cells from producing antibodies.

Recommended for you

Obese British man in court fight for surgery

Jul 11, 2011

A British man weighing 22 stone (139 kilograms, 306 pounds) launched a court appeal Monday against a decision to refuse him state-funded obesity surgery because he is not fat enough.

2008 crisis spurred rise in suicides in Europe

Jul 08, 2011

The financial crisis that began to hit Europe in mid-2008 reversed a steady, years-long fall in suicides among people of working age, according to a letter published on Friday by The Lancet.

New food labels dished up to keep Europe healthy

Jul 06, 2011

A groundbreaking deal on compulsory new food labels Wednesday is set to give Europeans clear information on the nutritional and energy content of products, as well as country of origin.

Overweight men have poorer sperm count

Jul 04, 2011

Overweight or obese men, like their female counterparts, have a lower chance of becoming a parent, according to a comparison of sperm quality presented at a European fertility meeting Monday.

User comments : 0