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[The role of NF-kappaB transcription factor in chronic viral hepatitis C and B].

Essential data pertaining to the structure and function of selected transcription factors such as NFAT, AP-1 and NF-kappaB in particular, are presented in the relation to viral hepatitis C and B. In chronic hepatitis C the activation of NF-kappaB is markedly modulated by viral proteins such as core protein and nonstructural ones, particularly NS5A and NS3. In hepatitis B the major factor influencing NF-kappaB function appears to be HBx protein. Effects of viral proteins on NF-kappaB function in relation to the course of hepatitis are complex. They participate in the perpetuation of inflammator

Use of bacteriophage MS2 as an internal control in viral reverse transcription-PCR assays.

Diagnostic systems based on reverse transcription (RT)-PCR are widely used for the detection of viral genomes in different human specimens. The application of internal controls (IC) to monitor each step of nucleic acid amplification is necessary to prevent false-negative results due to inhibition or human error. In this study, we designed various real-time RT-PCRs utilizing the coliphage MS2 replicase gene, which differ in detection format, amplicon size, and efficiency of amplification. These noncompetitive IC assays, using TaqMan, hybridization probe, or duplex scorpion probe techniques, wer

PRRSV-induced glucose-6-phosphate transporter promotes viral replication by suppressing type I interferon transcription.

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) leads to significant economic losses for the global swine industry. Screening and identification of PRRSV-regulated host proteins, followed by the development of long-acting anti-PRRSV therapeutics targeting these genetically stable host factors, represents a mainstream research direction in this field. Glucose-6-phosphate transporter (G6PT) is a core regulator of glucose uptake. However, its role in PRRSV infection remains unknown. Here, we report for the first time that PRRSV infection significantly upregulated

Sp140L функционирует как фактор ограничения герпесвируса, подавляющий вирусную транскрипцию и активирующий интерферонально-стимулированные гены.

Герпесвирусы, включая вирус Эпштейн-Барр (ЭБВ), - человеческий онкогенный вирус и важнейший пусковой механизм множественного склероза, - должны обходить механизмы ДНК-разведки, чтобы установить пожизненную скрытую инфекцию. Поэтому герпесвирусы кодируют вирусные белки, чтобы разрушить ключевые факторы, связанные с зондированием ДНК и вирусным ограничением. Первый вирусный белок латентности, выраженный EBNA-LP, крайне важен для преобразования наивных клеток B и установления вирусного генного экспрессии, однако его роль в уклонении от защиты хостов остается неясной. Используя одноклеточную после

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… Consistent with a previous report with an ORF3-KO of a C-strain HVS ( 22 ), knockout of SP100 rescued viral transcription after ORF3-KO HVS infection ( Fig. 7 B and C ). … Loss of SP100 or SP140L in the context of WT HVS infection had little or no effect on viral transcription ( SI Appendix , Fig. S8 D – F ) suggesting that ORF3 antagonizes both Sp100 and Sp140L function during WT HVS infection. …

The transcription factor Fli1 restricts the formation of memory precursor NK cells during viral infection.

Natural killer (NK) cells are innate lymphocytes that possess traits of adaptive immunity, such as memory formation. However, the molecular mechanisms by which NK cells persist to form memory cells are not well understood. Using single-cell RNA sequencing, we identified two distinct effector NK cell (NKeff) populations following mouse cytomegalovirus infection. Ly6C- memory precursor (MP) NK cells showed enhanced survival during the contraction phase in a Bcl2-dependent manner, and differentiated into Ly6C+ memory NK cells. MP NK cells exhibited distinct transcriptional and epigenetic signatur

A recombinant rabies virus carrying GFP between N and P affects viral transcription in vitro.

Several studies have demonstrated the rabies virus to be a perfect potential vaccine vector to insert foreign genes into the target genome. For this study, a green fluorescent protein (GFP) gene was cloned into the rabies virus (RABV) genome between the N and P gene. CT dinucleotide was inserted as intergenic region. The recombinant high egg passage Flury strain (HEP-Flury) of RABV, carrying GFP (rHEP-NP-GFP), was generated in BHK-21 cells using reverse genetics. According to the viral growth kinetics assay, the addition of GFP between N and P gene has little effect on the viral growth compare

The transcription factor IRF3 triggers "defensive suicide" necrosis in response to viral and bacterial pathogens.

Although molecular components that execute noninflammatory apoptotic cell death are well defined, molecular pathways that trigger necrotic cell death remain poorly characterized. Here, we show that in response to infection with adenovirus or Listeria monocytogenes, macrophages in vivo undergo rapid proinflammatory necrotic death that is controlled by interferon-regulatory factor 3 (IRF3). The transcriptional activity of IRF3 is, surprisingly, not required for the induction of necrosis, and it proceeds normally in mice deficient in all known regulators of necrotic death or IRF3 activation, incl

The dynein light chain 8 binding motif of rabies virus phosphoprotein promotes efficient viral transcription.

Recent studies indicate that the interaction between rabies virus (RV) phosphoprotein and the dynein light chain 8 (LC8) is essential for RV … prevented onset of RV-induced CNS disease. However, deletion of the LC8-BD significantly attenuated viral transcription and replication in the CNS. Studies in RAG2 knockout (KO) mice infected with the same recombinant RVs confirmed this finding and indicated that the adaptive immune system is not a factor in the attenuation of viral replication early in the infection …

Activation of STAT1 transcription factor precedes up-regulation of coxsackievirus-adenovirus receptor during viral myocarditis.

The coxsackievirus-adenovirus receptor (CAR) was originally described as a transmembrane protein involved in viral infection and was later found to be required for normal heart development. However, the role of CAR in virus-induced myocarditis has not been investigated so far. The purpose of this study was to assess myocardial CAR expression in response to cytokine-induced inflammatory reactions during the course of coxsackievirus-induced myocarditis. In Balb/c mice intraperitoneally infected with either 2x10(4) plaque-forming units (PFUs) of coxsackie B3 virus (CVB3) or 10(2) PFUs CVB3, CAR e

Insights of HIV-1 and HBV transcriptional regulation by viral transactivator Tat and HBx.

Transcriptions of nascent HIV-1 RNA from the integrated proviral DNA, and HBV RNAs from a stably formed minichromosome of cccDNA, are carried out by cellular RNA polymerase II, and strongly regulated by viral transactivation proteins Tat and HBx, respectively. Both Tat and HBx are intrinsically disordered proteins with promiscuous gene transactivation activities and regulate HIV-1 and HBV transcription by multiple, but similar mechanisms. The antiviral therapies of HIV-1 and HBV effectively suppress viral replication and enable the infection into latent states. The viral life cycles of HIV-1 a

Functional characterization of viral transcriptional regulators reveals extensive rewiring of host pathways.

Viral transcriptional regulators (vTRs) reprogram host gene regulatory networks to promote replication, persistence, and immune evasion. Despite the identification of hundreds of vTRs in human viruses, how they rewire host pathways remains unclear. Here, we systematically profiled 95 vTRs from diverse human viruses across multiple functional assays. vTRs perturb immune, cell proliferation/death, and signaling pathways through various mechanisms; some bind DNA directly, others cooperate or antagonize human transcription factors (hTFs), and some remodel chromatin. vTRs can act as activators or r…

HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication.

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) persists despite a vigorous virus-specific host immune response, and causes adult T-cell leukemia and lymphoma in approximately 2% of infected individuals. Here we report that HTLV-1 has evolved a genetic function to restrict its own replication by a novel post-transcriptional mechanism. The HTLV-1-encoded p30(II) is a nuclear-resident protein that binds to, and retains in the nucleus, the doubly spliced mRNA encoding the Tax and Rex proteins. Because Tex and Rex are positive regulators of viral gene expression, their inhibition by p30(II) r

Human filarial infection reshapes CD8+ T-cell transcription and function at homeostasis and following viral activation.

The role of CD8+ T cells in filarial infections remains poorly understood. Given the chronic nature of these infections, individuals living in endemic regions are frequently exposed to other pathogens including viruses. Because CD8 cells are essential for antiviral immunity, understanding how filarial infections shape the cytotoxic compartment is essential to elucidate their impact on bystander immunity. We evaluated the phenotype and function of CD8+ T cells from Loa loa-infected (Fil+) and -uninfected (Fil-) individuals at baseline and following cytomegalovirus (CMV) re-stimulation. Filarial

Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression.

Herpes simplex virus type 1 (HSV-1) is a major human pathogen with significant morbidity in neonates and immunocompromised individuals. However, antiviral drugs targeting HSV-1 are emerging with antiviral resistance, highlighting the need to identify new targets for future treatment. Once HSV-1 enters the host cells, it recruits host factors to facilitate viral life cycle. In this study, we showed that aryl hydrocarbon receptor (AhR), a ligand-activated nuclear receptor, is required for HSV-1 effective replication and offers an opportunity for pharmacological intervention. Our results showed t

NF-YA transcription factors suppress jasmonic acid-mediated antiviral defense and facilitate viral infection in rice.

NF-Y transcription factors are known to play many diverse roles in the development and physiological responses of plants but little is known about their role in plant defense. Here, we demonstrate the negative roles of rice NF-YA family genes in antiviral defense against two different plant viruses, Rice stripe virus (RSV, Tenuivirus) and Southern rice black-streaked dwarf virus (SRBSDV, Fijivirus). RSV and SRBSDV both induced the expression of OsNF-YA family genes. Overexpression of OsNF-YAs enhanced rice susceptibility to virus infection, while OsNF-YAs RNAi mutants were more resistant. Tran

The forkhead transcription factor Foxo3 negatively regulates natural killer cell function and viral clearance in myocarditis.

AIMS: Foxo3 is a transcription factor involved in cell metabolism, survival, and inflammatory disease. However, mechanistic insight in Foxo3 effects is still limited. Here, we investigated the role of Foxo3 on natural killer (NK) cell responses and its effects in viral myocarditis. METHODS AND RESULTS: Effects of Foxo3 on viral load and immune responses were investigated in a model of coxsackie virus B3 myocarditis in wild-type (WT) and Foxo3 deficient mice. Reduced immune cell infiltration, viral titres, and pro-inflammatory cytokines in cardiac tissue were observed in Foxo3-/- mice 7 days p

Quantitative limits of host-driven HIV transcription and host gene control by the viral transactivator Tat.

HIV transcription is amplified by the viral transactivator Tat, yet two quantitative issues remain unresolved in chromatin: the extent to which host machinery sustains transcription in the absence of Tat, and why Tat's widespread chromatin association yields limited host-gene output. We engineered an isogenic Tat-deficient derivative of the HIVGKO dual-reporter virus that preserves native proviral architecture, enabling longitudinal measurements across diverse integration sites in primary CD4⁺ T cells and Jurkat cells. Across thousands of proviruses, host factors alone supported a restricted b

Activation of E2F-dependent transcription by the mouse cytomegalovirus M117 protein affects the viral host range.

Cytomegaloviruses (CMVs) have a highly restricted host range as they replicate only in cells of their own or closely related species. To date, the molecular mechanisms underlying the CMV host restriction remain poorly understood. However, it has been shown that mouse cytomegalovirus (MCMV) can be adapted to human cells and that adaptation goes along with adaptive mutations in several viral genes. In this study, we identify MCMV M117 as a novel host range determinant. Mutations in this gene enable the virus to cross the species barrier and replicate in human RPE-1 cells. We show that the M117 p

Adenovirus E1A Activation Domain Regulates H3 Acetylation Affecting Varied Steps in Transcription at Different Viral Promoters.

How histone acetylation promotes transcription is not clearly understood. Here, we confirm an interaction between p300 and the adenovirus 2 large E1A activation domain (AD) and map the interacting regions in E1A by observing colocalization at an integrated lacO array of fusions of LacI-mCherry to E1A fragments with YFP-p300. Viruses with mutations in E1A subdomains were constructed and analyzed for kinetics of early viral RNA expression and association of acetylated H3K9, K18, K27, TBP, and RNA polymerase II (Pol II) across the viral genome. The results indicate that this E1A interaction with

Roles of serine and threonine residues of mumps virus P protein in viral transcription and replication.

UNLABELLED: Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe encephalitis. Vaccination against mumps virus has been effective in reducing mumps cases. However, recently large outbreaks have occurred in vaccinated populations. There is no anti-MuV drug. Understanding replication of MuV may lead to novel antiviral strategies. MuV RNA-dependent RNA polymerase minimally consists of the phosphoprotein (P) and the large protein (L). The P protei