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HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression.

Klase Z, Winograd R, Davis J, Carpio L, Hildreth R, Heydarian M, Fu S, McCaffrey T, Meiri E, Ayash-Rashkovsky M, Gilad S, Bentwich Z, Kashanchi F - Retrovirology (2009)

Bottom Line: Specifically, the microRNA down-regulates ERCC1 and IER3, protecting the cell from apoptosis.Comparison to our cloned sequence reveals possible target sites for the TAR miRNA as well.The TAR microRNA is expressed in all stages of the viral life cycle, can be detected in latently infected cells, and represents a mechanism wherein the virus extends the life of the infected cell for the purpose of increasing viral replication.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Department of Microbiology, Immunology and Tropical Medicine program, The George Washington University School of Medicine, Washington, District of Columbia 20037, USA. bcmzak@gwumc.edu

ABSTRACT

Background: RNA interference is a gene regulatory mechanism that employs small RNA molecules such as microRNA. Previous work has shown that HIV-1 produces TAR viral microRNA. Here we describe the effects of the HIV-1 TAR derived microRNA on cellular gene expression.

Results: Using a variation of standard techniques we have cloned and sequenced both the 5' and 3' arms of the TAR miRNA. We show that expression of the TAR microRNA protects infected cells from apoptosis and acts by down-regulating cellular genes involved in apoptosis. Specifically, the microRNA down-regulates ERCC1 and IER3, protecting the cell from apoptosis. Comparison to our cloned sequence reveals possible target sites for the TAR miRNA as well.

Conclusion: The TAR microRNA is expressed in all stages of the viral life cycle, can be detected in latently infected cells, and represents a mechanism wherein the virus extends the life of the infected cell for the purpose of increasing viral replication.

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Related in: MedlinePlus

Infected T-cell lines are resistant to apoptosis. CEM (A, B) and ACH2 (C, D) were cultured in the presence of 10% serum (A, C) or 0.1% serum (B, D) for 96 hours. Cells were then collected and apoptosis determined via AnnexinV and PI co-staining. Data are representative of three experiments.
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Figure 4: Infected T-cell lines are resistant to apoptosis. CEM (A, B) and ACH2 (C, D) were cultured in the presence of 10% serum (A, C) or 0.1% serum (B, D) for 96 hours. Cells were then collected and apoptosis determined via AnnexinV and PI co-staining. Data are representative of three experiments.

Mentions: Like the HLM-1s, the HIV-1 infected ACH-2 cells exhibited a resistance to serum starvation induced apoptosis. When stressed, the levels of apoptosis in ACH-2 cells increased less than in their uninfected control (CEM). According to the flow cytometry analysis of the cell populations, after 96 hours of serum starvation the CEM cells increased in their apoptotic level by 30% whereas the ACH-2 cells increased in apoptosis by only 10% (Fig 4 compare panel B to A and C to D).


HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression.

Klase Z, Winograd R, Davis J, Carpio L, Hildreth R, Heydarian M, Fu S, McCaffrey T, Meiri E, Ayash-Rashkovsky M, Gilad S, Bentwich Z, Kashanchi F - Retrovirology (2009)

Infected T-cell lines are resistant to apoptosis. CEM (A, B) and ACH2 (C, D) were cultured in the presence of 10% serum (A, C) or 0.1% serum (B, D) for 96 hours. Cells were then collected and apoptosis determined via AnnexinV and PI co-staining. Data are representative of three experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654423&req=5

Figure 4: Infected T-cell lines are resistant to apoptosis. CEM (A, B) and ACH2 (C, D) were cultured in the presence of 10% serum (A, C) or 0.1% serum (B, D) for 96 hours. Cells were then collected and apoptosis determined via AnnexinV and PI co-staining. Data are representative of three experiments.
Mentions: Like the HLM-1s, the HIV-1 infected ACH-2 cells exhibited a resistance to serum starvation induced apoptosis. When stressed, the levels of apoptosis in ACH-2 cells increased less than in their uninfected control (CEM). According to the flow cytometry analysis of the cell populations, after 96 hours of serum starvation the CEM cells increased in their apoptotic level by 30% whereas the ACH-2 cells increased in apoptosis by only 10% (Fig 4 compare panel B to A and C to D).

Bottom Line: Specifically, the microRNA down-regulates ERCC1 and IER3, protecting the cell from apoptosis.Comparison to our cloned sequence reveals possible target sites for the TAR miRNA as well.The TAR microRNA is expressed in all stages of the viral life cycle, can be detected in latently infected cells, and represents a mechanism wherein the virus extends the life of the infected cell for the purpose of increasing viral replication.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Department of Microbiology, Immunology and Tropical Medicine program, The George Washington University School of Medicine, Washington, District of Columbia 20037, USA. bcmzak@gwumc.edu

ABSTRACT

Background: RNA interference is a gene regulatory mechanism that employs small RNA molecules such as microRNA. Previous work has shown that HIV-1 produces TAR viral microRNA. Here we describe the effects of the HIV-1 TAR derived microRNA on cellular gene expression.

Results: Using a variation of standard techniques we have cloned and sequenced both the 5' and 3' arms of the TAR miRNA. We show that expression of the TAR microRNA protects infected cells from apoptosis and acts by down-regulating cellular genes involved in apoptosis. Specifically, the microRNA down-regulates ERCC1 and IER3, protecting the cell from apoptosis. Comparison to our cloned sequence reveals possible target sites for the TAR miRNA as well.

Conclusion: The TAR microRNA is expressed in all stages of the viral life cycle, can be detected in latently infected cells, and represents a mechanism wherein the virus extends the life of the infected cell for the purpose of increasing viral replication.

Show MeSH
Related in: MedlinePlus