Navigation Links
Mutant host cell protein sequesters critical HIV-1 element
Date:1/15/2009

Scientists have identified a new way to inhibit a molecule that is critical for HIV pathogenesis. The research, published by Cell Press in the January 16th issue of the journal Molecular Cell, presents a target for development of antiretroviral therapeutics that are likely to complement existing therapies and provide additional protection from HIV and AIDS.

Infection of human cells with HIV-1 requires multiple events that involve complex interactions between viral elements and cellular proteins. The virus must copy key parts of its DNA as mRNA molecules through a process called transcription. The mRNA molecules must be properly "spliced", or rearranged, and then transported out of the cell nucleus and into the cytoplasm where the mRNAs can be "translated" into viral proteins.

"Although there has been a great deal of effort directed at understanding HIV-1 transcription, mRNA splicing and nuclear export, little is known about the translational control of HIV-1 RNA in the cytoplasm," says senior study author, Dr. Johnny J. He from the Center for AIDS Research at Indiana University School of Medicine.

Dr. He and colleagues examined a protein called HIV-1 Nef that is translated from completely spliced HIV-1 RNA. Nef is very important for HIV pathogenesis and AIDS disease. "It is highly conceivable that intervention with Nef expression may complement the current anti-HIV therapies that are mainly targeted at HIV-1 protease and reverse transcriptase, providing a better treatment outcome," explains Dr. He.

The researchers found that a mutant form of Src-associated protein in mitosis of 68kDa (Sam68), a host cellular protein involved in HIV-1 pathogenesis, specifically interacts with nef mRNA and directly suppresses Nef expression. This particular Sam68 mutant was previously shown to inhibit HIV-1 replication by overriding its wild-type counterpart's function in nuclear export of unspliced and incompletely spliced HIV RNA. However, the mutant Sam68 was present in the cytoplasm, suggesting that it may serve some function in the cytoplasmic stage of the HIV-1 life cycle.

The ability of the Sam68 cytoplasmic mutant to interfere with Nef correlated with its ability to induce stress granules in the cytoplasm. Stress granules regulate gene expression at the translational level in response to a variety of external stimuli. Importantly, nef mRNA was targeted to and enriched in the stress granules.

"Taken together, these results demonstrate that stress granule induction and nef mRNA sequestration account for this translational suppression of Nef expression and offers a new strategy for development of anti-HIV therapeutics to buttress our fight against HIV/AIDS," concludes Dr. He.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related biology news :

1. Mutant sperm guide clinicians to new diseases
2. Mutant gene identified as villain in hardening of the arteries
3. MIT researchers offer glimpse of rare mutant cells
4. No helicopter moms among Rutgers mutant mice
5. Protein chatter linked to cancer activation
6. Scientists link fragile X tremor/ataxia syndrome to binding protein in RNA
7. Researchers identify proteins involved in new neurodegenerative syndrome
8. Low levels of key protein may indicate pancreatic cancer risk
9. Structure of 450 million year old protein reveals evolutions steps
10. Scientists retrace evolution with first atomic structure of an ancient protein
11. Specific brain protein required for nerve cell connections to form and function
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/4/2017)... 2017  CES 2017 – Valencell , the ... announced the launch of two new versions of ... biometric sensor modules that incorporate the best of ... expertise. The two new designs include Benchmark BE2.0, ... and Benchmark BW2.0, a 2-LED version of its ...
(Date:12/22/2016)... -- As part of its longstanding mission to improve genetic literacy ... released its latest children,s book, titled The One ... topics of inheritance and variation of traits that are part ... school classrooms in the US. The book ... Killoran , whose previous book with 23andMe, You ...
(Date:12/20/2016)... The rising popularity of mobility services ... stoking significant interest in keyless access systems. Following ... energy (BLE), biometrics and near-field communication (NFC) are ... wireless technologies in the automotive industry. This evolution ... systems opens the market to specialist companies such ...
Breaking Biology News(10 mins):
(Date:1/18/2017)... , Jan. 18, 2017 /PRNewswire/ - SQI ... sciences and diagnostics company that develops and commercializes ... ("SQI" or the "Company"), today announced that ... Inc. ("Kingsdale"), has resigned from its Board of ... changes to securities regulations that have limited both ...
(Date:1/17/2017)... ... January 17, 2017 , ... ... Factor (RF) to its VALIDATE® SP2 calibration verification / linearity test kit. VALIDATE® ... serum base. Each VALIDATE® SP2 kit is prepared using the CLSI recommended “equal ...
(Date:1/17/2017)... The Global Implantable Biomaterials Market is ... 7.5% over the next decade to reach approximately ... trends that the market is witnessing include increasing ... transplant surgeries and medical implants and technological advancements. ... into immunomodulatory biomaterials, natural, polymers, hydrogels and ceramics. ...
(Date:1/17/2017)... -- Roka Bioscience, Inc. (NASDAQ: ROKA ), a molecular ... of foodborne pathogens today announced the appointment of Mary Duseau ... , the Company,s President and CEO since 2009, who will assume ... changes are effective today. In addition, Ms. Duseau will ... ...
Breaking Biology Technology: