scholarly journals HIV- 1:  To Splice Or Not To Splice, That Is THE Question

2021 ◽  
Author(s):  
Ronald Swanstrom ◽  
Ann Emery
Keyword(s):  
Fitness Cost ◽  
Full Length ◽  
Regulatory Sequences ◽  
Supporting Evidence ◽  
Control Mechanisms ◽  
Genomic Rna ◽  
Cis Acting ◽  
Splicing Regulators ◽  
Mrna Transcripts ◽  
Hiv 1

HIV-1 transcribes only one kind of transcript – the full length genomic RNA. To make the mRNA transcripts for the accessory proteins Tat and Rev, the genomic RNA must completely splice. The mRNA transcripts for Vif, Vpr, and Env must splice but not completely.  Genomic RNA (which also functions as mRNA for the Gag and Gag/Pro/Pol precursor polyproteins) must not splice at all.  HIV-1 can tolerate a surprising range in the relative abundance of individual transcript types, and a surprising amount of aberrant and even odd splicing; however, it must not over-splice, which results in the loss of full length genomic RNA and has a dramatic fitness cost.  Loss of full length genomic transcripts through over-splicing has a dramatic fitness cost.  Cells typically do not tolerate unspliced/incompletely spliced transcripts, so HIV-1 has to circumvent this cell policing mechanism to allow some splicing while suppressing most.  Splicing is controlled by RNA secondary structure, cis-acting regulatory sequences which bind splicing factors, and the viral protein Rev.  There is still much work to be done to clarify the combinatorial effects of these splicing regulators.  These control mechanisms represent attractive targets to induce over-splicing as an antiviral strategy. Finally, splicing has been implicated in latency, but to date there is little supporting evidence for such a mechanism. In this review we apply what is known of cellular splicing to understand splicing in HIV-1, and also present data from our newer and more sensitive deep sequencing assays quantifying the different HIV-1 transcript types.

scholarly journals HIV-1: To Splice or Not to Splice, That Is the Question

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 181
Author(s):  
Ann Emery ◽  
Ronald Swanstrom
Keyword(s):  
Full Length ◽  
Regulatory Sequences ◽  
Supporting Evidence ◽  
Control Mechanisms ◽  
Genomic Rna ◽  
Cis Acting ◽  
Splicing Regulators ◽  
Individual Transcript ◽  
Mrna Transcripts ◽  
Hiv 1

The transcription of the HIV-1 provirus results in only one type of transcript—full length genomic RNA. To make the mRNA transcripts for the accessory proteins Tat and Rev, the genomic RNA must completely splice. The mRNA transcripts for Vif, Vpr, and Env must undergo splicing but not completely. Genomic RNA (which also functions as mRNA for the Gag and Gag/Pro/Pol precursor polyproteins) must not splice at all. HIV-1 can tolerate a surprising range in the relative abundance of individual transcript types, and a surprising amount of aberrant and even odd splicing; however, it must not over-splice, which results in the loss of full-length genomic RNA and has a dramatic fitness cost. Cells typically do not tolerate unspliced/incompletely spliced transcripts, so HIV-1 must circumvent this cell policing mechanism to allow some splicing while suppressing most. Splicing is controlled by RNA secondary structure, cis-acting regulatory sequences which bind splicing factors, and the viral protein Rev. There is still much work to be done to clarify the combinatorial effects of these splicing regulators. These control mechanisms represent attractive targets to induce over-splicing as an antiviral strategy. Finally, splicing has been implicated in latency, but to date there is little supporting evidence for such a mechanism. In this review we apply what is known of cellular splicing to understand splicing in HIV-1, and present data from our newer and more sensitive deep sequencing assays quantifying the different HIV-1 transcript types.

scholarly journals Tomato Bushy Stunt Virus Genomic RNA Accumulation Is Regulated by Interdependent cis-Acting Elements within the Movement Protein Open Reading Frames

2002 ◽  
Vol 76 (24) ◽  
pp. 12747-12757 ◽  
Author(s):  
Jong-Won Park ◽  
Bénédicte Desvoyes ◽  
Herman B. Scholthof
Keyword(s):  
Movement Protein ◽  
Regulatory Element ◽  
Inhibitory Effect ◽  
Tomato Bushy Stunt Virus ◽  
Open Reading Frames ◽  
Regulatory Sequences ◽  
Genomic Rna ◽  
Cis Acting ◽  
Hairpin Loops ◽  
Rna Accumulation

ABSTRACT This study on Tomato bushy stunt virus identified and defined three previously unknown regulatory sequences involved in RNA accumulation that are located within the 3′-proximal nested movement protein genes p22 and p19. The first is a 16-nucleotide (nt) element termed III-A that is positioned at the very 3′ end of p22 and is essential for RNA accumulation. Approximately 300 nt upstream of III-A resides an ∼80-nt inhibitory element (IE) that is obstructive to replication only in the absence of a third regulatory element of ∼30 nt (SUR-III) that is positioned immediately upstream of III-A. Inspection of the nucleotide sequences predicted that III-A and SUR-III can form looped hairpins. A comparison of different tombusviruses showed, in each case, conservation for potential base pairing between the two predicted hairpin-loops. Insertion of a spacer adjacent to the predicted hairpins had no or a minimal effect on RNA accumulation, whereas an insertion in the putative III-A loop abolished genomic RNA multiplication. We conclude that the sequences composing the predicted III-A and SUR-III hairpin-loops are crucial for optimal RNA accumulation and that the inhibitory effect of IE surfaces when the alleged interaction between SUR-III and III-A is disturbed.

scholarly journals An epitranscriptomic switch at the 5′-UTR controls genome selection during HIV-1 genomic RNA packaging

2019 ◽  
Author(s):  
Camila Pereira-Montecinos ◽  
Daniela Toro-Ascuy ◽  
Cecilia Rojas-Fuentes ◽  
Sebastián Riquelme-Barrios ◽  
Bárbara Rojas-Araya ◽  
...  
Keyword(s):  
Full Length ◽  
Genomic Rna ◽  
Rna Packaging ◽  
Gag Protein ◽  
Rna Molecules ◽  
Viral Genomes ◽  
Viral Particles ◽  
Demethylase Activity ◽  
Retroviral Replication ◽  
Hiv 1

ABSTRACTDuring retroviral replication, the full-length RNA serves both as mRNA and genomic RNA (gRNA). While the simple retrovirus MLV segregates its full-length RNA into two functional populations, the HIV-1 full-length RNA was proposed to exist as a single population used indistinctly for protein synthesis or packaging. However, the mechanisms by which the HIV-1 Gag protein selects the two RNA molecules that will be packaged into nascent virions remain poorly understood. Here, we demonstrate that HIV-1 full-length RNA packaging is regulated through an epitranscriptomic switch requiring demethylation of two conserved adenosine residues present within the 5′-UTR. As such, while m6A deposition by METTL3/METTL14 onto the full-length RNA was associated with increased Gag synthesis and reduced packaging, FTO-mediated demethylation was required for the incorporation of the full-length RNA into viral particles. Interestingly, HIV-1 Gag associates with the RNA demethylase FTO in the nucleus and drives full-length RNA demethylation. Finally, the specific inhibition of the FTO RNA demethylase activity suppressed HIV-1 full-length RNA packaging. Together, our data propose a novel epitranscriptomic mechanism allowing the selection of the full-length RNA molecules that will be used as viral genomes.

Modeling the dynamics of the solvated SL1 domain of HIV-1 genomic RNA

Biopolymers ◽  
2003 ◽  
Vol 69 (1) ◽  
pp. 1-14 ◽  
Author(s):  
G. La Penna ◽  
D. Genest ◽  
A. Perico
Keyword(s):  
Genomic Rna ◽  
Hiv 1

HIV-1 mRNA Transcripts from Persistently Infected Human Fetal Astrocytes

1993 ◽  
Vol 693 (1 Pediatric AID) ◽  
pp. 324-326 ◽  
Author(s):  
WALTER J. ATWOOD ◽  
CARLO S. TORNATORE ◽  
KAREN MEYERS ◽  
EUGENE O. MAJOR
Keyword(s):  
Persistently Infected ◽  
Mrna Transcripts ◽  
Hiv 1

scholarly journals Fitness-Balanced Escape Determines Resolution of Dynamic Founder Virus Escape Processes in HIV-1 Infection

2015 ◽  
Vol 89 (20) ◽  
pp. 10303-10318 ◽  
Author(s):  
Justine E. Sunshine ◽  
Brendan B. Larsen ◽  
Brandon Maust ◽  
Ellie Casey ◽  
Wenje Deng ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Evolution ◽  
T Cell Responses ◽  
Fitness Cost ◽  
Viral Population ◽  
Cell Responses ◽  
Founder Virus ◽  
Ctl Escape ◽  
The Impact ◽  
Hiv 1

ABSTRACTTo understand the interplay between host cytotoxic T-lymphocyte (CTL) responses and the mechanisms by which HIV-1 evades them, we studied viral evolutionary patterns associated with host CTL responses in six linked transmission pairs. HIV-1 sequences corresponding to full-length p17 and p24gagwere generated by 454 pyrosequencing for all pairs near the time of transmission, and seroconverting partners were followed for a median of 847 days postinfection. T-cell responses were screened by gamma interferon/interleukin-2 (IFN-γ/IL-2) FluoroSpot using autologous peptide sets reflecting any Gag variant present in at least 5% of sequence reads in the individual's viral population. While we found little evidence for the occurrence of CTL reversions, CTL escape processes were found to be highly dynamic, with multiple epitope variants emerging simultaneously. We found a correlation between epitope entropy and the number of epitope variants per response (r= 0.43;P= 0.05). In cases in which multiple escape mutations developed within a targeted epitope, a variant with no fitness cost became fixed in the viral population. When multiple mutations within an epitope achieved fitness-balanced escape, these escape mutants were each maintained in the viral population. Additional mutations found to confer escape but undetected in viral populations incurred high fitness costs, suggesting that functional constraints limit the available sites tolerable to escape mutations. These results further our understanding of the impact of CTL escape and reversion from the founder virus in HIV infection and contribute to the identification of immunogenic Gag regions most vulnerable to a targeted T-cell attack.IMPORTANCERapid diversification of the viral population is a hallmark of HIV-1 infection, and understanding the selective forces driving the emergence of viral variants can provide critical insight into the interplay between host immune responses and viral evolution. We used deep sequencing to comprehensively follow viral evolution over time in six linked HIV transmission pairs. We then mapped T-cell responses to explore if mutations arose due to adaption to the host and found that escape processes were often highly dynamic, with multiple mutations arising within targeted epitopes. When we explored the impact of these mutations on replicative capacity, we found that dynamic escape processes only resolve with the selection of mutations that conferred escape with no fitness cost to the virus. These results provide further understanding of the complicated viral-host interactions that occur during early HIV-1 infection and may help inform the design of future vaccine immunogens.

trans-Activation of the HIV-1 LTR by the HIV-1 tat and HTLV-I tax proteins is mediated by different cis-acting sequences

Virology ◽  
1991 ◽  
Vol 182 (2) ◽  
pp. 874-878 ◽  
Author(s):  
Klaus Zimmermann ◽  
Marika Dobrovnik ◽  
Claudia Ballaun ◽  
Dorian Bevec ◽  
Joachim Hauber ◽  
...  
Keyword(s):  
Cis Acting ◽  
Hiv 1

scholarly journals Substance P enhances HIV-1 infection in human fetal brain cell cultures expressing full-length neurokinin-1 receptor

2013 ◽  
Vol 19 (3) ◽  
pp. 219-227 ◽  
Author(s):  
Lynnae Schwartz ◽  
Sergei V. Spitsin ◽  
John Meshki ◽  
Florin Tuluc ◽  
Steven D. Douglas ◽  
...  
Keyword(s):  
Substance P ◽  
Cell Cultures ◽  
Fetal Brain ◽  
Brain Cell ◽  
Full Length ◽  
Human Fetal Brain ◽  
Neurokinin 1 Receptor ◽  
Brain Cell Cultures ◽  
Neurokinin 1 ◽  
Hiv 1

Tracing the origin and history of HIV-1 subtype B′ epidemic by near full-length genome analyses

AIDS ◽  
2012 ◽  
Vol 26 (7) ◽  
pp. 877-884 ◽  
Author(s):  
Zhe Li ◽  
Xiang He ◽  
Zhe Wang ◽  
Hui Xing ◽  
Fan Li ◽  
...  
Keyword(s):  
Full Length ◽  
Subtype B ◽  
History Of ◽  
Genome Analyses ◽  
Full Length Genome ◽  
Hiv 1

Reconstitution of the vitamin D-responsive osteocalcin transcription unit in Saccharomyces cerevisiae

1989 ◽  
Vol 9 (8) ◽  
pp. 3517-3523
Author(s):  
D P McDonnell ◽  
J W Pike ◽  
D J Drutz ◽  
T R Butt ◽  
B W O'Malley
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Vitamin D ◽  
Transcription Factors ◽  
Promoter Activity ◽  
Transcription Unit ◽  
Proximal Promoter ◽  
Regulatory Sequences ◽  
Cis Acting ◽  
Osteocalcin Gene ◽  
Definition Of

The human osteocalcin gene is regulated in mammalian osteoblasts by 1,25(OH)2D3-dependent and -independent mechanisms. The sequences responsible for this activity have been mapped to within the -1339 region of the gene. We show here that this enhancer region functions analogously in Saccharomyces cerevisiae cells engineered to produce active 1,25(OH)2D3 receptor. When fused to the proximal promoter elements of the yeast iso-1-cytochrome c gene, the enhancer demonstrated substantial promoter activity. This activity was elevated further by 1,25(OH)2D3 when the reporter constructs were assayed in cells containing the 1,25(OH)2D3 receptor. This system affords a model for 1,25(OH)2D3 action and represents a simple assay system that will enable definition of the important cis-acting regulatory sequences within the osteocalcin gene and identification of their cognate transcription factors.

Sign in / Sign up

Export Citation Format

Share Document