Discovery may lead to new HIV drugs, says Jefferson virologist

August 07, 2002

When scientists at London's King's College and their colleagues elsewhere uncovered the identity of a gene that prevents HIV from reproducing, but which is itself blocked by an HIV protein, they took a huge step in solving one of the great puzzles of the virus' biology.

What's more, the discovery, says virologist Roger J. Pomerantz, M.D., "could start a new genre of AIDS drugs."

Researchers found that a gene called CEM15 is a natural inhibitor of HIV, acting as a brake on HIV's development. They showed that biologically tying up a protein called Vif, or Virion infectivity factor, allows CEM15 to stop the virus from replicating.

Vif, then, could become "a new target against which we can develop HIV drugs," says Dr. Pomerantz, professor of medicine, biochemistry and molecular pharmacology and chief of the division of infectious diseases at Jefferson Medical College of Thomas Jefferson University in Philadelphia. His News and Views editorial and commentary accompanies a paper on the finding August 8, 2002 in the journal Nature.

"It's the first regulatory protein against which you might be able to develop an antiviral," says Dr. Pomerantz, who is also director of the Center for Human Virology at Jefferson Medical College.

Scientists have known about Vif since the mid 1980s, Dr. Pomerantz explains. Vif, he says, is a regulatory protein needed for the virus to grow and make infectious viruses, or particles, from certain cells, but not from others. "If researchers tried to grow virus in certain immune system cells, such as peripheral blood T cells, monocyte macrophages and many T cell lines from humans, they needed Vif or the viruses died." That is, the new viruses made by an infected T cell could not infect other cells.

More recently, they concluded that there was some unknown natural cellular defense factor that Vif was subverting.

But the question was, what was it about T cells and some other HIV targets that blocked the virus from replicating, and which Vif somehow neutralized? Now, the discovery of CEM15 solves the mystery. "HIV can't make infectious virus particles from T cells or macrophages without it," he says.

"If you can inhibit Vif, or stop it from inhibiting the CEM15 protein, you have a great antiviral," says Dr. Pomerantz, "Nothing in HIV will be infectious."

Much work lies ahead. Researchers, for example, still don't know exactly how Vif works. But learning how to stymie Vif's activity is crucial to allowing CEM15 to affect HIV. "The next step is to understand how Vif inhibits this cell protein," says Dr. Pomerantz, and what CEM15 normally does.
-end-
Contact: Steve Benowitz or
Phyllis Fisher
215/955-6300
After Hours: 215/955-6060

Thomas Jefferson University

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.