Gladstone and UCSF scientists provide a global view of how HIV/AIDS hijacks cells during infection

December 21, 2011

SAN FRANCISCO, CA--December 21, 2011--Gladstone Institutes scientist Nevan Krogan, PhD, today is announcing research that identifies how HIV--the virus that causes AIDS--hijacks the body's own defenses to promote infection. This discovery could one day help curb the spread of the HIV/AIDS pandemic.

Dr. Krogan conducted this research in his laboratory at the University of California, San Francisco (UCSF)--a leading medical school with which Gladstone is affiliated--where Dr. Krogan is an associate professor of cellular and molecular pharmacology and an affiliate of the California Institute for Quantitative Biosciences (QB3). Since joining Gladstone as an associate investigator in June, Dr. Krogan has served as a unique, collaborative bridge between the two institutions in the field of systems biology, an area in which scientists perform advanced, computational analysis of large-scale data sets that are drawn from complex biological systems.

In his companion papers being published online today in Nature, Dr. Krogan describes how HIV commandeers restriction factors--a class of human proteins that have evolved to block viruses such as HIV--to weaken the body's defenses and enhance the virulence of HIV infection.

"One of the keys to HIV's success is how quickly it can evolve new attack strategies--and the way in which it uses our own proteins against us is a prime example of that," said Dr. Krogan. "However, now that we've shed light on this complex process, we are one step closer to developing new drugs that will help us pull ahead in this evolutionary arms race."

AIDS has killed more than 25 million people around the world since first being identified some 30 years ago. In the United States alone, more than one million people live with HIV/AIDS at an annual cost of $34 billion. Dr. Krogan's experiments show promise for the development of more effective antiretroviral therapies for people with HIV. Further, they have laid the foundation for future research at Gladstone.

In his experiments, Dr. Krogan performed a two-part investigation of protein interactions. First, he conducted a systematic, global analysis of all potential interactions that occur between proteins made by the body (human proteins) and proteins made by the virus (HIV proteins). Second, he whittled down these ~500 interactions to the one that appeared most likely to fuel HIV infection: the interaction between the human protein CBFß and the HIV protein Vif.

Normally during HIV infection, a restriction factor called APOBEC3G acts as a molecular roadblock, preventing the virus from reaching its target--the CD4 T white blood cells that are a major component of the immune system. But Dr. Krogan found that when the HIV protein Vif binds to the human protein CBFß, Vif is strengthened and APOBEC3G degrades. This degradation weakens ABOBEC3G's ability to stop HIV and the virus is free to infect the CD4 T cells.

"This is the first comprehensive look at how HIV interacts globally with components of the cell," said Judith H. Greenberg, PhD, acting director of the National Institutes of Health's National Institute of General Medical Sciences, which partially supported this research through its AIDS-related structural biology program. "The work is a good example of how biophysical studies can improve our understanding of disease and point the way to the exploration of potential therapeutic targets."
-end-
Other groups at UCSF who participated in this research include the labs of John Gross, PhD, Andrej Sali, PhD, Alan Frankel, PhD, Alma Burlingame, PhD, Charles Craik, PhD, Ryan Hernandez, PhD, and Tanja Kortemme. Funding came from a wide variety of sources, including QB3, the Host Pathogen Circuitry Center at UCSF, the Searle Scholars Program, the W.M. Keck Foundation and the National Institutes of Health.

About UCSF

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For further information, please visit http://www.ucsf.edu/.



About the Gladstone Institutes

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent illness and cure patients suffering from cardiovascular disease, neurological disease, or viral infections. Gladstone is affiliated with the University of California, San Francisco.

Gladstone Institutes

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.