Navigation Links
Ancient immune defense mechanism is no match for HIV-1

Researchers have discovered that mammalian cells infected with HIV-1 engage a primitive defense mechanism that was previously observed only in plants and invertebrates. The research also reveals exactly how HIV-1 successfully thwarts this rare form of immunity in vertebrate cells. However, elucidation of the mechanism HIV-1 uses to protect itself provides some critical insight into a potential vulnerability within the HIV-1 molecule. Identification of what might be a long sought after weakness in the virus may have application for rational design of future anti-HIV-1 therapies. The study is published in the May issue of Immunity.

RNA silencing is a type of natural immune defense in which sequence-specific RNA degradation follows the recognition of double-stranded RNA (dsRNA). The dsRNA is processed by a protein called Dicer, which chops the long strands of RNA into smaller pieces, resulting in the production of an RNA-induced silencing complex (RISC). RISC can specifically identify and degrade complementary target RNA. This process is known as RNA interference (RNAi) and can silence the ability of a virus to successfully reproduce itself. Although this mechanism has been artificially manipulated to selectively inhibit specific genes in mammalian cells, it was not known whether mammalian viruses naturally elicit this type of immunity in vertebrate cells.

Drs. Yamina Bennasser and Kuan-Teh Jeang from the Molecular Virology Section at the National Institute of Allergy and Infectious Disease and colleagues found that infection with HIV-1 induces RNAi in human cells. However, the researchers discovered that HIV-1 has an intriguing strategy to combat this cellular defense. The HIV-1 protein Tat, well known as a transcriptional activator, also can function as a suppressor of RNA silencing (SRS). Tat helps HIV-1 to elude the cell's natural RNAi defense by interfering with the ability of Dicer to process dsRNAs.

"Our results suggest that the dynamic in terplay between RNAi and SRS remains physiologically conserved from plants and invertebrates to higher vertebrate animals," explains Dr. Jeang. "Our finding that Tat is an SRS also helps explain the long-standing biological observation that when HIV-1 is engineered to be lacking Tat but contains alternative transcriptional activators, it fails to spread productively in human cells." The researchers also suggest that their findings raise a challenge to proposed therapeutic strategies making use of RNAi. "Because HIV-1 evades all other RNAi by point mutations, we reason that its requirement for an SRS is solely to shield this last 'Achilles' heel that we think HIV-1 cannot alter for functional reasons. The sequence we describe may represent a viable target for RNAi that HIV-1 cannot elude by using the point mutation mechanism, " explains Dr. Jeang.

The researchers include Yamina Bennasser and Kuan-Teh Jeang of the National Institute of Allergy and Infectious Diseases; Shu-Yun Le of the National Cancer Institute; and Monsef Benkirane of the Institut de Genetique Humaine, CNRS.

Bennasser, Y., Le, S.-Y., Benkirane, M., and Jeang, K.-T. (2005). Evidence that HIV-1 Encodes an siRNA and a Suppressor of RNA Silencing. Immunity, 22, 607-619. http://www.immunity.com


'"/>

Source:Cell Press


Related biology news :

1. Ancient olfaction protein is shared by many bugs, offering new pest control target
2. Ancient DNA helps clarify the origins of two extinct New World horse species
3. Researchers Discover Ancient Origins Of Tuberculosis-causing Bacteria
4. Ancient DNA confirms single origin of Malagasy primates
5. Ancient anthropoid origins discovered in Africa
6. Ancient trans-Atlantic swarm brought locusts to the New World
7. Ancient humans brought bottle gourds to the Americas from Asia
8. Ancient DNA helps UF researchers unearth potential hemophilia therapy
9. Ancient DNA provides clues to the evolution of social behavior
10. Ancient ants arose 140-168 million years ago
11. Ancient fossil DNA found preserved in crystal
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:8/21/2019)... ... August 21, 2019 , ... ... line for rapid and low-cost biomanufacturing of complex protein therapeutics, today announced the ... of AbSci's Scientific Advisory Board, Dr. Larimore brings more than 30 years of ...
(Date:8/21/2019)... (PRWEB) , ... August 20, 2019 , ... ... experience for the second time since BioInformatics first fielded the survey in 2016. ... Life Science Customer Experience , from BioInformatics, part of Science and Medicine Group. ...
(Date:8/15/2019)... (PRWEB) , ... August 15, 2019 , ... Deep ... of their Food and Agriculture practice, a new unit dedicated to building 100 companies ... sustainable nutrition, raw materials and supply chains. , Deep Science Ventures was founded ...
Breaking Biology News(10 mins):
(Date:8/27/2019)... ... August 27, 2019 , ... Dr. Kim Carlson is a veterinary surgeon ... Peninsula Veterinary Surgical Group , a new surgical practice in San Mateo. She ... and add more veterinary specialists as the practice grows. , When asked about the ...
(Date:8/23/2019)... ... August 22, 2019 , ... An upcoming episode of ... to broadcast 4Q/2019. Check your local listings for more information. , This segment ... delivery. Focusing on therapeutics for children and the elderly, viewers will learn about ...
(Date:8/8/2019)... FRANCISCO (PRWEB) , ... August 08, 2019 , ... ... Intelligent Virtual Agents for sales and service organizations, today announced that the ... Value Leadership Award for the IVA market . Inference will officially accept the ...
(Date:8/6/2019)... DEERFIELD, Ill. (PRWEB) , ... August 05, 2019 ... ... announced that Jason Casarella has been recognized as a distinguished leader by PharmaVOICE ... is featured in an article in the magazine’s July/August special issue. , As ...
Breaking Biology Technology: