Change In HIV May Precipitate AIDS

March 12, 1998

Scientists at the National Institute of Child Health and Human Development (NICHD) have developed a new model for studying the destructive effects of AIDS in live tissue samples. The critical events in the development of AIDS take place in lymphoid tissue, but AIDS research has been hampered by the fact that an animal model of HIV infection that readily mimics human AIDS does not exist. Scientists also lack readily available laboratory techniques for closely mimicking, in vitro, HIV infection in the body (in vivo).

The NICHD scientists have overcome this limitation by culturing and infecting pieces of tonsil, which is composed largely of lymphoid tissue, obtained from tonsillectomies. With this advance, they have helped illuminate one of the central questions of HIV pathology--what triggers the eventual development of AIDS in people who carry HIV?

The finding appears in the March issue of Nature Medicine, and was reported by scientists Svetlana Glushakova, Jean-Charles Grivel, Wendy Fitzgerald, Andrew Sylvester, Joshua Zimmerberg, and Leonid Margolis.

The laboratory model, which allows HIV to be studied in the tissue in which it is usually found, consists of tiny (1mm) cubes of tonsil cultured on wet collagen sponges. The cubes, which retain their viability and native architecture for several weeks, can be infected with HIV (which multiplies and spills into the surrounding medium), so that they mount a response to immunological challenge. Such responses are the hallmark of lymphoid tissue. Thus, just as they would in the body, the blocks of lymphoid tissue make antibodies to tetanus toxoid or diphtheria toxoid (which are used to immunize people against tetanus and diphtheria), and they do so with much greater efficiency than isolated immune cells, underscoring the importance of the cell's environment to the cell's proper functioning.

With the help of these cultured, immunologically responsive, tonsil blocks, the NICHD team has started to answer some of the basic questions about AIDS and HIV infection. HIV is transmitted by a form of the virus that can infect macrophages, scavenger cells that live in the body's tissues, and other immune cells known as CD4+ T lymphocytes. Viruses with this property are called M-tropic (M for macrophage) and are the predominant form of HIV found in a person's body early in the disease process. Later in the course of the disease, a different strain of the virus often predominates, and that strain is called "T-tropic," because it attacks T lymphocytes almost exclusively.

Researchers speculate whether AIDS develops partly because of the transition from M-tropism to T-tropism. In the Nature Medicine paper, the researchers present strong evidence that it is a change in the virus itself that leads to irreparable damage to the immune system.

Dr. Margolis and his coworkers showed that, after being infected with T-tropic viruses, the response of the tonsil blocks to immunological challenge is suppressed, whereas M-tropic viruses have the opposite effect, making the blocks secrete more antibody. This study supports the view that changes in the properties of HIV may contribute to the immunologic deterioration that leads to AIDS.

This is a useful tool for scientists to observe the development of immunodeficiency outside the body. The technique promises to provide important information about HIV pathogenesis and should be extremely useful in developing and testing therapies and vaccination strategies.
-end-


NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.