In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Q: Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses.

A: Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone
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Q: Influenza infection is a major cause of morbidity and mortality worldwide, especially during pandemics outbreaks. Emerging data indicate that phase II antioxidant enzyme pathways could play a role in virusassociated inflammation and immune clearance. While Nrf2-dependent gene expression is known to modify inflammation, a mechanistic role in viral susceptibility and clearance has yet to be elucidated. Therefore, we utilized differentiated human nasal epithelial cells (NEC) and an enzymatic virus-like particle entry assay, to examine the role Nrf2-dependent gene expression has on viral entry and replication. Herein, lentiviral vectors that express Nrf2-specific short hairpin (sh)-RNA effectively decreased both Nrf2 mRNA and Nrf2 protein expression in transduced human NEC from healthy volunteers. Nrf2 knockdown correlated with a significant increase in influenza virus entry and replication. Conversely, supplementation with the potent Nrf2 activators sulforaphane (SFN) and epigallocatechin gallate (EGCG) significantly decreased viral entry and replication. The suppressive effects of EGCG on viral replication were abolished in cells with knocked-down Nrf2 expression, suggesting a causal relationship between the EGCG-induced activation of Nrf2 and the ability to protect against viral infection. Interestingly, the induction of Nrf2 via nutritional supplements SFN and EGCG increased antiviral mediators/responses: RIG-I, IFN-, and MxA at baseline in the absence of infection. Our data indicate that there is an inverse relationship between the levels of Nrf2 expression and the viral entry/ replication. We also demonstrate that supplementation with Nrf2-activating antioxidants inhibits viral replication in human NEC, which may prove to be an attractive therapeutic intervention. Taken together, these data indicate potential mechanisms by which Nrf2-dependent gene expression regulates susceptibility to influenza in human epithelial cells.

A: Nrf2 expression modifies influenza A entry and replication in nasal epithelial cells
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Q: Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infection worldwide. The absence of a commercial vaccine and the limited success of current therapeutic strategies against RSV make further research necessary. We used a multi-cohort analysis approach to investigate host transcriptomic biomarkers and shed further light on the molecular mechanism underlying RSV-host interactions. We meta-analyzed seven transcriptome microarray studies from the public Gene Expression Omnibus (GEO) repository containing a total of 922 samples, including RSV, healthy controls, coronaviruses, enteroviruses, influenzas, rhinoviruses, and coinfections, from both adult and pediatric patients. We identified > 1500 genes differentially expressed when comparing the transcriptomes of RSV-infected patients against healthy controls. Functional enrichment analysis showed several pathways significantly altered, including immunologic response mediated by RSV infection, pattern recognition receptors, cell cycle, and olfactory signaling. In addition, we identified a minimal 17-transcript host signature specific for RSV infection by comparing transcriptomic profiles against other respiratory viruses. These multi-genic signatures might help to investigate future drug targets against RSV infection. remain unknown [10] . The notable impact of pediatric respiratory diseases produced by RSV in the health system raises the need for a more in-depth understanding of the molecular mechanism responsible for the host susceptibility to the infection. This would improve the development of new preventive, diagnostic, and therapeutic strategies, which could reduce the social, medical, and economic burden of the disease [11] . In the era of personalized medicine and molecular diagnostics, the study of host transcriptomics during infection is becoming an important tool not only for the study of the host-pathogen interaction but also for the diagnosis and prognosis of diseases. In the last few years, some host expression signatures related to both infectious [12] [13] [14] [15] [16] and non-infectious diseases [17, 18] have been reported. However, most of the studies are focused only on particular cohorts from a certain ethnicity or population group and restricted geographic areas, from a specific age group and the same epidemic period. Moreover, these studies compare patients against healthy controls without investigating the impact of other respiratory pathogens on the host transcriptome. Moreover, the technical noise inherent to microarray data, together with the usually small (underpowered) cohorts analyzed in individual studies, often lead to unreliable, inconsistent and non-reproducible results, probably due to type I and type II errors [19, 20] . Instead, a multi-cohort study allows increasing sample size and statistical power, leading to more accurate and conclusive findings and, thus, facilitating the implementation of the results into a molecular test [21] [22] [23] [24] . By compiling different datasets from respiratory diseases-related host transcriptomic studies available in public resources we aimed at investigating specific expression signatures allowing to differentiate RSV respiratory infection from other viral respiratory infections and also healthy controls. We also explored the role of the differentially expressed genes (DEG) in RSV-infected patients and related pathways in the context of RSV infection.

A:
A Meta-Analysis of Multiple Whole Blood Gene Expression Data Unveils a Diagnostic Host-Response Transcript Signature for Respiratory Syncytial Virus
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