scholarly journals The N-Terminal and Central Domains of CoV-2 nsp1 Play Key Functional Roles in Suppression of Cellular Gene Expression and Preservation of Viral Gene Expression

2021 ◽  
Author(s):  
Aaron S. Mendez ◽  
Michael Ly ◽  
Angélica M. González-Sánchez ◽  
Ella Hartenian ◽  
Nicholas T. Ingolia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Cellular Gene ◽  
Cellular Gene Expression ◽  
Functional Roles

scholarly journals The N-terminal domain of SARS-CoV-2 nsp1 plays key roles in suppression of cellular gene expression and preservation of viral gene expression

Cell Reports ◽  
2021 ◽  
pp. 109841
Author(s):  
Aaron S. Mendez ◽  
Michael Ly ◽  
Angélica M. González-Sánchez ◽  
Ella Hartenian ◽  
Nicholas T. Ingolia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Cellular Gene ◽  
Cellular Gene Expression ◽  
Terminal Domain

scholarly journals The N-terminal and central domains of CoV-2 nsp1 play key functional roles in suppression of cellular gene expression and preservation of viral gene expression

2021 ◽  
Author(s):  
Aaron Stephen Mendez ◽  
Michael Ly ◽  
Angélica M. González-Sánchez ◽  
Ella Hartenian ◽  
Nicholas Ingolia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mutational Analysis ◽  
Nonstructural Protein ◽  
Ribosomal Subunit ◽  
Viral Gene ◽  
Viral Mrna ◽  
Cellular Gene ◽  
Cellular Gene Expression ◽  
Nonstructural Protein 1

Nonstructural protein 1 (nsp1) is the first viral protein synthesized during coronavirus (CoV) infection and is a key virulence factor that dampens the innate immune response. It restricts cellular gene expression through a combination of inhibiting translation by blocking the mRNA entry channel of the 40S ribosomal subunit and by promoting mRNA degradation. We performed a detailed structure-guided mutational analysis of CoV-2 nsp1 coupled with in vitro and cell-based functional assays, revealing insight into how it coordinates these activities against host but not viral mRNA. We found that residues in the N-terminal and central regions of nsp1 not involved in docking into the 40S mRNA entry channel nonetheless stabilize its association with the ribosome and mRNA, thereby enhancing its restriction of host gene expression. These residues are also critical for the ability of mRNA containing the CoV-2 leader sequence to escape translational repression. Notably, we identify CoV-2 nsp1 mutants that gain the ability to repress translation of viral leader-containing transcripts. These data support a model in which viral mRNA binding functionally alters the association of nsp1 with the ribosome, which has implications for drug targeting and understanding how engineered or emerging mutations in CoV-2 nsp1 could attenuate the virus.

Cellular gene expression programming algorithm based on stack decoding method

2010 ◽  
Vol 29 (12) ◽  
pp. 3280-3282
Author(s):  
Liu YANG ◽  
Pei HE ◽  
Xiao-hai PAN
Keyword(s):  
Gene Expression ◽  
Gene Expression Programming ◽  
Programming Algorithm ◽  
Cellular Gene ◽  
Cellular Gene Expression

scholarly journals Latency Reversing Agents: Kick and Kill of HTLV-1?

2021 ◽  
Vol 22 (11) ◽  
pp. 5545
Author(s):  
Annika P. Schnell ◽  
Stephan Kohrt ◽  
Andrea K. Thoma-Kress
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Viral Gene Expression ◽  
Cytotoxic T Cell ◽  
Viral Gene ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Reversing Agents ◽  
Ctl Responses

Human T-cell leukemia virus type 1 (HTLV-1), the cause of adult T-cell leukemia/lymphoma (ATLL), is a retrovirus, which integrates into the host genome and persistently infects CD4+ T-cells. Virus propagation is stimulated by (1) clonal expansion of infected cells and (2) de novo infection. Viral gene expression is induced by the transactivator protein Tax, which recruits host factors like positive transcription elongation factor b (P-TEFb) to the viral promoter. Since HTLV-1 gene expression is repressed in vivo by viral, cellular, and epigenetic mechanisms in late phases of infection, HTLV-1 avoids an efficient CD8+ cytotoxic T-cell (CTL) response directed against the immunodominant viral Tax antigen. Hence, therapeutic strategies using latency reversing agents (LRAs) sought to transiently activate viral gene expression and antigen presentation of Tax to enhance CTL responses towards HTLV-1, and thus, to expose the latent HTLV-1 reservoir to immune destruction. Here, we review strategies that aimed at enhancing Tax expression and Tax-specific CTL responses to interfere with HTLV-1 latency. Further, we provide an overview of LRAs including (1) histone deacetylase inhibitors (HDACi) and (2) activators of P-TEFb, that have mainly been studied in context of human immunodeficiency virus (HIV), but which may also be powerful in the context of HTLV-1.

scholarly journals The [KIL-d] Element Specifically Regulates Viral Gene Expression in Yeast

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 601-609 ◽  
Author(s):  
Zsolt Tallóczy ◽  
Rebecca Mazar ◽  
Denise E Georgopoulos ◽  
Fausto Ramos ◽  
Michael J Leibowitz
Keyword(s):  
Gene Expression ◽  
Phenotypic Expression ◽  
Viral Gene Expression ◽  
Virus Genome ◽  
Viral Rna ◽  
High Rate ◽  
Viral Gene ◽  
Double Stranded Rna ◽  
Yeast Prions ◽  
Killer Virus

Abstract The cytoplasmically inherited [KIL-d] element epigenetically regulates killer virus gene expression in Saccharomyces cerevisiae. [KIL-d] results in variegated defects in expression of the M double-stranded RNA viral segment in haploid cells that are “healed” in diploids. We report that the [KIL-d] element is spontaneously lost with a frequency of 10−4–10−5 and reappears with variegated phenotypic expression with a frequency of ≥10−3. This high rate of loss and higher rate of reappearance is unlike any known nucleic acid replicon but resembles the behavior of yeast prions. However, [KIL-d] is distinct from the known yeast prions in its relative guanidinium hydrochloride incurability and independence of Hsp104 protein for its maintenance. Despite its transmissibility by successive cytoplasmic transfers, multiple cytoplasmic nucleic acids have been proven not to carry the [KIL-d] trait. [KIL-d] epigenetically regulates the expression of the M double-stranded RNA satellite virus genome, but fails to alter the expression of M cDNA. This specificity remained even after a cycle of mating and meiosis. Due to its unique genetic properties and viral RNA specificity, [KIL-d] represents a new type of genetic element that interacts with a viral RNA genome.

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