Cryptic proteins translated from deletion-containing viral genomes dramatically expand the influenza virus proteome.

Productive infections by RNA viruses require faithful replication of the entire genome. Yet many RNA viruses also produce deletion-containing viral genomes (DelVGs), aberrant replication products with large internal deletions. DelVGs interfere with the replication of wild-type virus and their presence in patients is associated with better clinical outcomes.

Successful Treatment of Rapidly Progressive Interstitial Lung Disease in Juvenile Dermatomyositis.

Juvenile dermatomyositis (JDM) is a rare systemic autoimmune disease characterized by cutaneous findings, muscle inflammation, and vasculopathy. Patients with antimelanoma differentiation associated gene 5 (anti-MDA5) JDM may have subtle muscle weakness, absence of pathognomonic rashes, and more polyarthritis and ulcerative skin lesions when compared with other JDM subtypes. Although there is a known association of rapidly progressive interstitial lung disease (RP-ILD) in patients with anti-MDA5 dermatomyositis, few case reports describe this association in the pediatric literature.

Non-criteria antiphospholipid antibodies and calprotectin as potential biomarkers in pediatric antiphospholipid syndrome.

Our study aimed to evaluate the presence, clinical associations, and potential mechanistic roles of non-criteria antiphospholipid antibodies (aPL) and circulating calprotectin, a highly stable marker of neutrophil extracellular trap release (NETosis), in pediatric APS patients. We found that 79% of pediatric APS patients had at least one non-criteria aPL at moderate-to-high titer. Univariate logistic regression demonstrated that positive anti-beta-2 glycoprotein I domain 1 (anti-D1) IgG (p = 0.

Superinfection exclusion creates spatially distinct influenza virus populations.

Interactions between viruses during coinfections can influence viral fitness and population diversity, as seen in the generation of reassortant pandemic influenza A virus (IAV) strains. However, opportunities for interactions between closely related viruses are limited by a process known as superinfection exclusion (SIE), which blocks coinfection shortly after primary infection. Using IAVs, we asked whether SIE, an effect which occurs at the level of individual cells, could limit interactions between populations of viruses as they spread across multiple cells within a host.

The Antiphospholipid Syndrome in the Pediatric Population.

Pediatric antiphospholipid syndrome (APS) is characterized by autoantibodies directed against protein complexes on cellular membranes and leads to a prothrombotic, proinflammatory state. A child with APS may present with venous, arterial, or small vessel thrombosis. Other manifestations of APS include nonthrombotic manifestations, such as hematologic and neurologic symptoms.

Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection.

The induction of antiviral effector proteins as part of a homeostatically controlled innate immune response to infection plays a critical role in limiting the propagation and transmission of respiratory pathogens. However, the prolonged induction of this immune response can lead to lung hyperinflammation, tissue damage, and respiratory failure. We hypothesized that tissues exposed to the constant threat of infection may constitutively express higher levels of antiviral effector proteins to reduce the need to activate potentially harmful innate immune defences.

Identifying additional risk factors for arterial and venous thrombosis among pediatric antiphospholipid antibodies carriers.

Background: Antiphospholipid antibodies (aPL) have been extensively reported in children, but investigations into thrombotic risks associated with aPL positivity in pediatric patients is scarce. Positive aPL are not uncommon in pediatric connective tissue diseases (CTD), but identification and management of these patients is challenging due to lack of validated criteria and a paucity of data. In this study, we identify potential additional risk factors for thrombosis in a unique cohort of pediatric aPL positive carriers.

Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection.

RNA viruses are a major human health threat. The life cycles of many highly pathogenic RNA viruses like influenza A virus (IAV) and Lassa virus depends on host mRNA, because viral polymerases cleave 5'-m7G-capped host transcripts to prime viral mRNA synthesis ("cap-snatching"). We hypothesized that start codons within cap-snatched host transcripts could generate chimeric human-viral mRNAs with coding potential.

MORC3, a Component of PML Nuclear Bodies, Has a Role in Restricting Herpes Simplex Virus 1 and Human Cytomegalovirus.

Unlabelled: We previously reported that MORC3, a protein associated with promyelocytic leukemia nuclear bodies (PML NBs), is a target of herpes simplex virus 1 (HSV-1) ICP0-mediated degradation (E. Sloan, et al., PLoS Pathog 11:e1005059, 2015, http://dx.

Analysis of the SUMO2 Proteome during HSV-1 Infection.

Covalent linkage to members of the small ubiquitin-like (SUMO) family of proteins is an important mechanism by which the functions of many cellular proteins are regulated. Sumoylation has roles in the control of protein stability, activity and localization, and is involved in the regulation of transcription, gene expression, chromatin structure, nuclear transport and RNA metabolism. Sumoylation is also linked, both positively and negatively, with the replication of many different viruses both in terms of modification of viral proteins and modulation of sumoylated cellular proteins that influence the efficiency of infection.

Health-related quality of life in small-cell lung cancer: a systematic review on reporting of methods and clinical issues in randomised controlled trials.

Small-cell lung cancer represents about 15% of all lung cancers; increasingly, randomised controlled trials of this disease measure the health-related quality of life of patients. In this Systematic Review we assess the adequacy of reporting of health-related quality-of-life methods in randomised controlled trials of small-cell lung cancer, and the potential effect of this reporting on clinical decision making. Although overall reporting of health-related quality of life was acceptable, improvements are needed to optimise the use of health-related quality of life in randomised controlled trials.

The viral ubiquitin ligase ICP0 is neither sufficient nor necessary for degradation of the cellular DNA sensor IFI16 during herpes simplex virus 1 infection.

The cellular protein IFI16 colocalizes with the herpes simplex virus 1 (HSV-1) ubiquitin ligase ICP0 at early times of infection and is degraded as infection progresses. Here, we report that the factors governing the degradation of IFI16 and its colocalization with ICP0 are distinct from those of promyelocytic leukemia protein (PML), a well-characterized ICP0 substrate. Unlike PML, IFI16 colocalization with ICP0 was dependent on the ICP0 RING finger and did not occur when proteasome activity was inhibited.

Varicella-zoster virus inhibition of the NF-κB pathway during infection of human dendritic cells: role for open reading frame 61 as a modulator of NF-κB activity.

Dendritic cells (DC) are antigen-presenting cells essential for initiating primary immune responses and therefore an ideal target for viral immune evasion. Varicella-zoster virus (VZV) can productively infect immature human DCs and impair their function as immune effectors by inhibiting their maturation, as evidenced by the expression modulation of functionally important cell surface immune molecules CD80, CD86, CD83, and major histocompatibility complex I. The NF-κB pathway largely regulates the expression of these immune molecules, and therefore we sought to determine whether VZV infection of DCs modulates the NF-κB pathway.

Health-related quality of life in non-small-cell lung cancer: an update of a systematic review on methodologic issues in randomized controlled trials.

Purpose: This study is an update of a systematic review of health-related quality-of-life (HRQOL) methodology reporting in non-small-cell lung cancer (NSCLC) randomized controlled trials (RCTs). The objective was to evaluate HRQOL methodology reporting over the last decade and its benefit for clinical decision making.

Methods: A MEDLINE systematic literature review was performed.

Myc, mondo, and metabolism.

The Myc family of proto-oncogenes plays a central role in tumorigenesis, yet identifying the specific transcriptional targets required for its oncogenic function remains a challenge. Given Myc's broad role in transcriptional regulation, it seems unlikely that there exists one or even a small set of Myc effectors strictly required for transformation. Over the last decade or so, it has become clear that Myc can drive several metabolic pathways associated with cell growth.