Expression of the human immunodeficiency virus type 1 primer binding sequence inhibits HIV-1 replication

Human Gene Therapy
A M KechliK S Slobod

Abstract

Optimal targets for anti-human immunodeficiency virus (HIV) moieties are those regions of the viral genome that are greatly conserved. The primer binding site (PBS) of HIV is an 18-nucleotide sequence complementary to the 3' end of tRNA(Lys3) that serves as the primer for HIV-1 reverse transcription. All HIV-1 isolates analyzed to date contain a PBS complementary to tRNA(Lys3) illustrating the conservation of this sequence. We investigated the activity of a hammerhead ribozyme targeting the PBS of HIV-1. CEMss cells transduced with retroviral vectors containing either the PBS hammerhead ribozyme or its complementary sequence (as a control) in the R region of the vector long terminal repeat (LTR) were challenged with HIV-1NL4-3. Surprisingly >80% inhibition of HIV-1 production was observed with the vector containing the (control) sequence complementary to the PBS ribozyme. We propose that the LTR-driven vector transcript containing 18 nucleotides identical to the HIV-1 PBS may act like an RNA decoy to titrate viral proteins such as reverse transcriptase and nucleocapsid away from genuine viral transcripts, thus compromising virus replication.

References

Nov 21, 1986·Cell·D JohnsonM Chao
Nov 1, 1995·Human Gene Therapy·H I Miller

❮ Previous
Next ❯

Citations

Dec 12, 2001·HIV Medicine·N Dorman, A M Lever
May 5, 2010·World Journal of Gastroenterology : WJG·Robert SmolicGeorge Y Wu
Oct 23, 2004·Pathology, Research and Practice·Edenilson Eduardo CaloreL V de Almeida
Dec 23, 2014·Cytokine & Growth Factor Reviews·Zulema Antonia PercarioElisabetta Affabris

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.