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 HIV. 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 cell structure element actin and the cell’s ability to move. Thus, the affected immune cells 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 AIDS 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.

Source:
Prof. Dr. Oliver T. Fackler

University Hospital Heidelberg

Patient / Public:
Health Professional:
Article Opinions:	0 posts

South Africa’s shortage of health professionals combined with a budget shortfall of over $130 million for the government’s HIV programs could keep the country from reaching its goal of providing 80 percent of the people living with HIV/AIDS in need of treatment with antiretroviral drugs (ARVs) by 2011, South African Health Minister Aaron Motsoaledi said on Tuesday, Reuters reports. Motsoaledi said of the funding, “We have discussed it with Treasury, calculated the costs and I have already met international funders. We are waiting and hoping that there is no chance of the actual shortfall happening.”

According to Motsoaledi, an estimated 700,000 HIV-positive South African’s currently receive ARVs. “Unfortunately it is only 50 percent of the number that has been targeted,” he told Reuters. The article examines the factors contributing to the shortage of health professionals in South Africa, including trained professionals leaving the country for positions that offer higher pay and better conditions, and the low number of doctors being trained in the country compared to those needed annually.

According to Reuters, “[d]espite his overstretched budget, Motsoaledi is exploring providing ARVs to patients” earlier than when currently dispensed by public hospitals. “Waiting for people to go to a CD4 count of 200 is too low too late, maybe we should start them at 350,” Motsoaledi said (Govender, 9/15).

This information was reprinted from globalhealth.kff.org with kind permission from the Henry J. Kaiser Family Foundation. You can view the entire Kaiser Daily Global Health Policy Report, search the archives and sign up for email delivery at globalhealth.kff.org.

© Henry J. Kaiser Family Foundation. All rights reserved.

On September 18, six leading sexual health and HIV organisations are launching SHout loud (Sexual Health out loud) http://www.shoutloud.org.uk , a website which enables the general public, community groups and campaigners to have their say about sexual health, contraception and HIV services in England.

The new site, launching during sexual health week, is a joint initiative by the African HIV Policy Network (AHPN), Brook, fpa, the Medical Foundation for AIDS and Sexual Health (MedFASH), NAT (National AIDS Trust) and Terrence Higgins Trust. Visitors type in their postcode to receive local data about sexual health, find out if sexual health is a priority in their area and can use the site to take action by contacting key decision-makers.

Everyone who is interested in sexual health will be encouraged to get involved from young people, to those living with or affected by HIV to anyone who feels it’s an issue worth shouting about.

Teenage pregnancy rates are high across particular areas in England, one in 12 young people has chlamydia and more people are living with HIV than ever before. Individuals and community groups will be encouraged to get in touch with their MP, Primary Care Trust (PCT) and local authority to demonstrate that these issues matter to them and to try and ensure that sexual health, HIV and contraception services get the attention and funding they deserve.

Sophie Robinson, SHout loud project officer said “Some people are embarrassed to talk about sexual health, which often means that they don’t express their views about local services to help them improve. The SHout loud website gives people the opportunity to show that sexual health issues really matter to them and to campaign for support and investment. If you care about the subject, sign up now and get your voice heard.”

Getting local people engaged in campaigning on local healthcare priorities is essential, especially during a recession when resources are limited.

Individuals and community groups can join the site to get information and ideas on how to get involved. To sign up visit http://www.shoutloud.org.uk

Notes

- The African HIV Policy Network (AHPN) is an alliance of various African community-based organisations and their members who collaboratively work for fair policies for people living with or affected by HIV/AIDS in the UK, providing various services such as training, support, research and information. AHPN is the only organisation within the UK whose work is dedicated to policy, advocacy and representation at national level, its main focus being HIV and the Sexual Health of Africans in the UK.

- Brook helps young people to make informed, active choices about their personal and sexual relationships so they can enjoy their sexuality without harm. Brook is the UK’s leading provider of sexual health services and advice for all young people under 25 and provides free and confidential sexual health information, contraception, pregnancy testing, advice and counselling, testing and treatment for sexually transmitted infections and outreach and education work, reaching around 210,000 young people every year. Brook has 45 years of experience working with young people and currently has a network of services in England, Scotland, Northern Ireland and Jersey.

- fpa is one of the UK’s leading sexual health charities. Its mission is to help establish a society in which everyone has positive, informed and non-judgmental attitudes to sex and relationships; where everyone can make informed choice about sex and reproduction so that they can enjoy sexual health free from prejudice and harm. fpa provides a range of information, education and support services and runs public awareness and high profile media campaigns on all aspects of sexual health. For more information go to http://www.fpa.org.uk

- The Medical Foundation for AIDS & Sexual Health (MedFASH) is a charity dedicated to the pursuit of excellence in the healthcare of people affected by HIV, sexually transmitted infections and related conditions. It develops and disseminates information and practical guidance for health professionals and policy-makers, fosters communication and collaboration within and beyond the healthcare sector, and builds links between practice and policy.

- NAT (National AIDS Trust) is the UK’s leading charity dedicated to transforming society’s response to HIV. We provide fresh thinking, expert advice and practical resources. We campaign for change. Shaping attitudes. Challenging injustice. Changing lives. http://www.nat.org.uk

Source
Terrence Higgins Trust