Serendipity Bridges Gap Between Research On HIV Receptors And Antibodies

April 01, 1997

Philadelphia, Pa. -- The big news from the HIV basic research front in 1996 was the discovery by Penn researchers and others of a group of cell-surface receptor molecules that, along with the long-known receptor CD4, must be present for the virus to enter and infect cells of the immune system. The usual role of these receptors is to offer binding sites for various chemokines, a family of molecules involved in mediating immune responses; different HIV strains, however, have evolved to use the receptors for their purposes, too.

During the same period, James A. Hoxie, MD, an associate professor of medicine, and his coworkers developed an antibody against one of these important chemokine receptors, a molecule called CXCR4, or fusin, discovered at the National Institutes of Health -- although this fact was not immediately apparent to them.

The Penn scientists had originally set out to produce monoclonal antibodies to SIV, or simian immunodeficiency virus, which causes an AIDS-like disease in monkeys. To do this, they immunized mice with SIV-infected cells and screened antibodies derived from the mice for the ability to block infection by the virus in cell lines. While they were successful in producing a number of antibodies against SIV in this way, they also inadvertently stumbled upon an antibody that was able to block infection but that reacted with the cell rather than with the virus. When this antibody, termed 12G5, was also shown to block some types of HIV from infecting cells, they redoubled their efforts to identify the molecule with which 12G5 was reacting. Following the lead that CXCR4 was required by some viruses to infect cells, they checked to see if 12G5 reacted with CXCR4 and were pleasantly surprised to find that it did.

The new antibody represented the first anti-CXCR4 antibody and has since made many new studies involving this molecule possible. As a tool, the antibody has enormous value to HIV investigators, as evidenced by the fact that Hoxie has so far supplied it on request to about 250 other laboratories around the world.

"Our discovery of this antibody was somewhat serendipitous, but now we're up and running with a unique reagent that has been extremely useful to many laboratories" says Hoxie. In the March 4 issue of the Proceedings of the National Academy of Sciences, for example, researchers at Harvard Medical School and LeukoSite Inc. used Hoxie's antibody and one against another chemokine receptor known as CCR5 to create a detailed hypothesis describing how HIV infection leads to the slow, progressive destruction of the immune system.

-- Dr. James A. Hoxie can be reached at (215) 898-0261.

The University of Pennsylvania Medical Center's sponsored research ranks fifth in the United States, based on grant support from the National Institutes of Health, the primary funder of biomedical research in the nation -- $149 million in federal fiscal year 1996. In addition, for the second consecutive year, the institution posted the highest growth rate in its research activity -- 9.1 percent -- of the top ten U.S. academic medical centers during the same period. Penn news releases are available to reporters by direct e-mail, fax, or U.S. mail, upon request. They are also posted electronically to EurekAlert! (, an Internet resource sponsored by the American Association for the Advancement of Science, and to the SciNews-MedNews section of the Journalism Forum, a component of CompuServe. Additionally, they are distributed via the electronic news service Quadnet. [hoxie.rel]

University of Pennsylvania School of Medicine

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 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