Navigation Links
Cold Spring Harbor scientists reveal a protein's role in enabling AIDS virus to reproduce

A team of scientists at Cold Spring Harbor Laboratory (CSHL) has discovered new details about how a simian strain of the AIDS virus replicates. The findings are significant because they suggest new strategies to prevent replication, and because they are applicable to human strains of the virus, which, despite the persistent efforts of scientists over two decades, can only be slowed by drug treatments but neither cured nor prevented.

Jacek Skowronski, Ph.D., CHSL associate professor, led a team that studied a virulent strain of simian immune-deficiency (SIV) virus called SIVsm/mac, named for two species of monkeys in which it occurs, sooty mangabeys and macaques. The team included members of Dr. Skowronskis CSHL lab and researchers at Stowers Institute for Medical Research in Kansas City, Missouri, and the Skirball Institute of Biomolecular Medicine in New York City.

Like versions of the virus that occur in humans, SIV viral particles, or virions, are composed of a few fundamental parts. At their heart are two identical but separate strands of RNA surrounded by a protective envelope of roughly 2,000 proteins called a capsid.

This tiny, conical capsule, in turn, is surrounded by multiple defensive rings, somewhat like the walls of a medieval city. Immediately surrounding it is a protective protein shell, or matrix, and beyond it a formidable double-walled viral envelope. Poking through the outer envelope are the viral equivalent of grappling hooks, protein molecules designed to lock onto receptors on the surface of the unfortunate cell that the virus will attach to and then invade.

Viruses Hijack Living Cells to Reproduce

Viruses, unlike cells, are not living things. They must penetrate a living cell and commandeer its internal machineries in order to reproduce. HIV and its simian cousin SIV are members of a viral subspecies called retroviruses that invert the usual reproductive procedure. Their genetic raw material is not DNA but rather RNA, and before they can begin to replicate, they must first convert their RNA into DNA, using a special enzyme that they encode, called reverse transcriptase.

Once its RNA has been reverse-transcribed into DNA, the virion, having invaded a cell whose genetic material consists of DNA, can shed its protein coat and immediately proceed to integrate its newly converted DNA -- containing 9 genes -- into the host cells DNA. In this way the virion effectively hijacks the cell and reproduces itself whenever the cell reproduces.

Dr. Skowronski has devoted years to the study of various molecular factors -- think of them as assistants -- that immune-deficiency viruses employ to perform a range of essential tasks. The idea behind his approach is to understand with great precision all of the details of the processes by which the virus lives and propagates, as a means of identifying points of vulnerability, where drugs might be inserted to foul up the works.

In the research just completed, results of which appeared in PLoS Pathogens on May 9, Skowronski and his team focused on a so-called accessory protein called Vpx (Viral protein x). Prior studies had shown that Vpx was produced by simian, as well as a subset of human, immunodeficiency viruses, and was somehow active at the heart of their reproductive processes in a subset of immune cells called macrophages. The question was how, and to what effect.

How Vpx Enables the Virus to Replicate

Macrophages are central players in the mammalian immune system. Immune-deficiency viruses are devastating because they specifically seek out, invade, and commandeer the machinery of these particular cells -- macrophages, dendritic cells, helper T-cells -- which protect the mammalian system from foreign invaders.

Skowronski and colleagues knew from prior work that Vpx was a key enabler: it somehow facilitated an early event in the viral life cycle that helped the virus invade macrophage target cells. Recent studies had further shown that Vpx proteins in both monkey and human viruses promoted the process of reverse transcription that underlies the conversion of viral RNA to DNA.

In their study, which consisted of several steps, the CSHL team showed that when the vpx gene (the gene that encodes the Vpx protein) was deliberately deleted, the virus went about reverse transcription very inefficiently.

This suggests that the Vpx protein is key to the process by which the virus infects macrophages, Dr. Skowronski comments, and further, that it seems to be acting either before and/or during the reverse transcription process. This new view of Vpxs role contrasts with a prior hypothesis that it was involved in the transporting of genetic material that had already undergone reverse transcription.

The teams experiments revealed that the Vpx protein in the SIVmac virus binds to a complex of three cellular proteins that in turn engage a molecular machinery involved in the degradation of proteins. Thus, the team revealed for the first time not only that Vpx interacted with this system -- called the ubiquitin-dependent proteosomal protein degradation mechanism -- but also identified precisely the way it does so, via a series of intermediate steps.

The net result, says Dr. Skowronski, is that we show how Vpx enables efficient reverse transcription in the simian virus, and in so doing, overcomes an innate block that otherwise prevents viral replication.

By implication, this suggests a strategy by which a future drug might interfere with the reproductive machinery of the virus to prevent or limit is ability to spread. There are no guarantees, of course, that such an approach will work, Dr. Skowronski says, but unless we understand molecular mechanisms such as this one that empower this remarkable virus, we are not likely to devise a means of stopping it.


Contact: Jim Bono
Cold Spring Harbor Laboratory

Related medicine news :

1. Eating junk food whilst pregnant and breastfeeding may lead to obese offspring
2. Adult offspring of parents with PTSD have lower cortisol levels
3. A classic method for modeling skin cancer is featured in Cold Spring Harbor Protocols
4. Parents PTSD May Boost Stress in Offspring
5. Partnership for a Drug-Free America and Colorado Springs Police Department Introduce Methamphetamine Prevention Program to Colorado Law Enforcement
6. International Consulting Firm Health Fitness Dynamics Hired to Oversee Springbrook Inns Planned New Spa
7. COLORBLENDS to Donate Portion of Sales of Spring Forward Daffodil Blend to the Christopher and Dana Reeve Foundation
8. Springer adds Advances in Therapy to journals portfolio
9. Lifespring Health Promotes Health and Fitness by Sponsoring Silicon Valley Marathon on November 3rd and 4th
10. Announcing Always Best Care Senior Services Expansion into Colorado Springs, Colorado
11. Cold Spring Harbor scientists devise novel, low-cost method of sifting genomes high-value regions
Post Your Comments:
(Date:11/30/2015)... ... 30, 2015 , ... The Progressive Dental Institute ... 29 and 30, 2016. The course welcomes dental professionals and members of their ... how to better succeed in the modern dental marketplace. The course combines presentations ...
(Date:11/30/2015)... , ... November 30, 2015 , ... ... key disease-causing component of bacteria could be effective in fighting methicillin-resistant Staphylococcus aureus ... State University. , Their study showed that small molecule analogs that target the ...
(Date:11/30/2015)... NJ (PRWEB) , ... November 30, 2015 , ... Dr. ... With three office locations, patients can visit Dr. Margulies to experience the best available ... to hold the title of "NJ Top Dentist"! , Orthodontics is the branch of ...
(Date:11/30/2015)... ... November 30, 2015 , ... ”Dying Words: The AIDS Reporting ... on December 1, 2015, to coincide with World AIDS Day. The multi-media project will ... covered the AIDS epidemic as he was dying of the disease. , A collaborative ...
(Date:11/30/2015)... ... November 30, 2015 , ... According to RF Safe, the ... scientist at Consumer Reports as supporting a “A Call for Clarity” on cell ... The original Nov 2015 CR story titled, “Does Cell-Phone Radiation Cause Cancer?” ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... -- Kevin Smith has been appointed Chief Commercial Officer ... wireless monitoring of vital signs.  As CCO based ... Smith will be responsible for the development and ... also directly oversee partnering with US hospitals and ... the first early warning detection device to be ...
(Date:11/30/2015)... Nov. 30, 2015  The fee-for-service reimbursement ... U.S. medical imaging is on its way ... care payer-provider contracts are set to phase ... wake, alter provider-vendor relationships. The shift to ... forward new purchasing frameworks in the medical ...
(Date:11/30/2015)... SAN DIEGO , Nov. 30, 2015 ... ARNA ) today announced that the U.S. Food ... New Drug Application (NDA) for an extended release formulation ... offer patients a chronic weight management treatment in a ... currently approved as an adjunct to a reduced-calorie diet ...
Breaking Medicine Technology: