Evaluation of immune sensor responses to a viral small noncoding RNA.

Introduction: Gammaherpesviruses are widespread pathogens causing persistent infections linked to the development of numerous types of lymphomas in humans. During latency, most of the viral protein-coding genes are suppressed, facilitating evasion of adaptive immune recognition of protein antigens. In contrast, many noncoding RNA (ncRNA) molecules are expressed in infected cells and can regulate key cellular pathways while simultaneously evading adaptive immune recognition.

High-density resolution of the Kaposi's sarcoma associated herpesvirus transcriptome identifies novel transcript isoforms generated by long-range transcription and alternative splicing.

Kaposi's sarcoma-associated herpesvirus is the etiologic agent of Kaposi's sarcoma and two B-cell malignancies. Recent advancements in sequencing technologies have led to high resolution transcriptomes for several human herpesviruses that densely encode genes on both strands. However, for KSHV progress remained limited due to the overall low percentage of KSHV transcripts, even during lytic replication.

Virology-the path forward.

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases.

Observed size distribution changes in American lobsters over a 12-year period in southwestern Nova Scotia, Canada.

Size distribution and size frequency information of American lobsters (Homarus americanus) are often used to help estimate the age distributions, and reproductive output for the species and to guide the determination of appropriate minimum legal sizes for the fishery. This study used truncated linear regression models to estimate the effects of sampling year, sampling month, lobster sex and water depth on the lobster size. A dataset of almost 130,000 trap-caught lobsters from the two most important lobster fishing areas of Atlantic Canada collected over a 12-year period (2004-2015) was analyzed.

B cell expression of E3 ubiquitin ligase Cul4b promotes chronic gammaherpesvirus infection .

The human gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus are etiologic agents of numerous B cell lymphomas. A hallmark of gammaherpesvirus infection is their ability to establish lifelong latency in B cells. However, the specific mechanisms that mediate chronic infection in B cells remain elusive.

Gammaherpesvirus-mediated repression reveals EWSR1 to be a negative regulator of B cell responses.

The germinal center (GC) plays a central role in the generation of antigen-specific B cells and antibodies. Tight regulation of the GC is essential due to the inherent risks of tumorigenesis and autoimmunity posed by inappropriate GC B cell processes. Gammaherpesviruses such as Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV68) utilize numerous armaments to drive infected naïve B cells, independent of antigen, through GC reactions to expand the latently infected B cell population and establish a stable latency reservoir.

Fisheries dataset on moulting patterns and shell quality of American lobsters H. americanus in Atlantic Canada.

Monitoring the moulting phenology of American lobsters (Homarus americanus) is important for maintaining sustainable lobster stocks. Changes in lobster landings can affect reproduction and disease susceptibility. Data on lobster moult indicators and on life-history traits (sex, size) were collated from a twelve-year monitoring program (2004-2015) in six lobster fishing areas in Atlantic Canada.

A Polymorphism in the Epstein-Barr Virus EBER2 Noncoding RNA Drives Expansion of Latently Infected B Cells.

The oncogenic gammaherpesviruses, including human Epstein-Barr virus (EBV), human Kaposi's sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68 (MHV68, γHV68, MuHV-4), are associated with numerous malignancies, including B cell lymphomas and nasopharyngeal carcinoma. These viruses employ numerous molecular strategies to colonize the host, including the expression of noncoding RNAs (ncRNAs). As the first viral ncRNAs identified, EBV-encoded RNA 1 and 2 (EBER1 and EBER2, respectively) have been investigated extensively for decades; however, their specific functions remain largely unknown.

Spatial and temporal patterns in the sex ratio of American lobsters (Homarus americanus) in southwestern Nova Scotia, Canada.

An approximate 1:1 sex ratio of American lobsters can be skewed due to environmental factors or fisheries management. Substantial skewness can impact mating behaviour and lower reproduction which could have far-reaching ecological and economic consequences. The aim was to investigate the sex ratio patterns of lobsters in two lobster fishing areas (LFAs) in southwestern Nova Scotia, Canada and identify factors associated with skewed sex ratios.

Conquering the Host: Determinants of Pathogenesis Learned from Murine Gammaherpesvirus 68.

Gammaherpesviruses are an important class of oncogenic pathogens that are exquisitely evolved to their respective hosts. As such, the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV) do not naturally infect nonhuman primates or rodents. There is a clear need to fully explore mechanisms of gammaherpesvirus pathogenesis, host control, and immune evasion in the host.

Empirical Validation of Overlapping Virus lncRNAs and Coding Transcripts by Northern Blot.

Viruses, like their metazoan hosts, have evolved to utilize intricate transcriptional mechanisms to generate a vast array of both coding and noncoding RNA transcripts. The resolution of specific noncoding RNA transcripts produced by viruses, particularly herpesviruses, presents a particularly difficult challenge due to their highly dense dsDNA genomes and their complex, overlapping, and context-dependent network of transcripts. While new long read sequencing platforms have facilitated the resolution of some noncoding transcripts from virus genomes, empirical molecular validation of transcripts from individual regions is essential.

EBV miRNAs are potent effectors of tumor cell transcriptome remodeling in promoting immune escape.

The Epstein Barr virus (EBV) contributes to the tumor phenotype through a limited set of primarily non-coding viral RNAs, including 31 mature miRNAs. Here we investigated the impact of EBV miRNAs on remodeling the tumor cell transcriptome. Strikingly, EBV miRNAs displayed exceptionally abundant expression in primary EBV-associated Burkitt's Lymphomas (BLs) and Gastric Carcinomas (GCs).

Immune protection is dependent on the gut microbiome in a lethal mouse gammaherpesviral infection.

Immunopathogenesis in systemic viral infections can induce a septic state with leaky capillary syndrome, disseminated coagulopathy, and high mortality with limited treatment options. Murine gammaherpesvirus-68 (MHV-68) intraperitoneal infection is a gammaherpesvirus model for producing severe vasculitis, colitis and lethal hemorrhagic pneumonia in interferon gamma receptor-deficient (IFNγR) mice. In prior work, treatment with myxomavirus-derived Serp-1 or a derivative peptide S-7 (GTTASSDTAITLIPR) induced immune protection, reduced disease severity and improved survival after MHV-68 infection.

Epstein-Barr virus EBER1 and murine gammaherpesvirus TMER4 share conserved in vivo function to promote B cell egress and dissemination.

The oncogenic gammaherpesviruses, including human Epstein-Barr virus (EBV), human Kaposi's sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68 (MHV68, γHV68, MuHV-4) establish life-long latency in circulating B cells. The precise determinants that mediate in vivo gammaherpesvirus latency and tumorigenesis remain unclear. The EBV-encoded RNAs (EBERs) are among the first noncoding RNAs ever identified and have been the subject of decades of studies; however, their biological roles during in vivo infection remain unknown.

Identification of murine gammaherpesvirus 68 miRNA-mRNA hybrids reveals miRNA target conservation among gammaherpesviruses including host translation and protein modification machinery.

Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), establish lifelong latent infection in B cells and are associated with a variety of tumors. In addition to protein coding genes, these viruses encode numerous microRNAs (miRNAs) within their genomes. While putative host targets of EBV and KSHV miRNAs have been previously identified, the specific functions of these miRNAs during in vivo infection are largely unknown.

A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) To Promote Latent Infection of Germinal Center B Cells.

Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), directly contribute to the genesis of multiple types of malignancies, including B cell lymphomas. , these viruses infect B cells and manipulate B cell biology to establish lifelong latent infection. To accomplish this, gammaherpesviruses employ an array of gene products, including microRNAs (miRNAs).

Genome-wide Transcript Structure Resolution Reveals Abundant Alternate Isoform Usage from Murine Gammaherpesvirus 68.

The gammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68 (MHV68, MuHV-4, γHV68), are etiologic agents of a wide range of lymphomas and non-hematological malignancies. These viruses possess large and highly dense dsDNA genomes that feature >80 bidirectionally positioned open reading frames (ORFs). The abundance of overlapping transcripts and extensive splicing throughout these genomes have until now prohibited high throughput-based resolution of transcript structures.

Gammaherpesvirus RNAs Come Full Circle.

After an adaptive immune response is mounted, gammaherpesviruses achieve persistence through the utilization of viral noncoding RNAs to craft a suitable host cell environment in an immunologically transparent manner. While gammaherpesvirus long noncoding RNAs (lncRNAs) and microRNAs have been recognized for some time and have been actively investigated, a recent spate of reports have now identified repertoires of the circular RNA (circRNA) class of noncoding RNAs in both the lymphocryptovirus and rhadinovirus genera of gammaherpesviruses. Despite the recent nature of these findings, the detection of circRNAs across viruses and viral gene expression programs, the conservation of some viral circRNAs, and their detection in the clinical setting already raises the spectrum of functional importance in gammaherpesvirus biology and associated malignancies.

Gammaherpesvirus Readthrough Transcription Generates a Long Non-Coding RNA That Is Regulated by Antisense miRNAs and Correlates with Enhanced Lytic Replication In Vivo.

Gammaherpesviruses, including the human pathogens Epstein⁻Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are oncogenic viruses that establish lifelong infections in hosts and are associated with the development of lymphoproliferative diseases and lymphomas. Recent studies have shown that the majority of the mammalian genome is transcribed and gives rise to numerous long non-coding RNAs (lncRNAs). Likewise, the large double-stranded DNA virus genomes of herpesviruses undergo pervasive transcription, including the expression of many as yet uncharacterized lncRNAs.

Comparative Analysis of Gammaherpesvirus Circular RNA Repertoires: Conserved and Unique Viral Circular RNAs.

Recent studies have identified circular RNAs (circRNAs) expressed from the Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) human DNA tumor viruses. To gain initial insights into the potential relevance of EBV circRNAs in virus biology and disease, we assessed the circRNAome of the interspecies homologue rhesus macaque lymphocryptovirus (rLCV) in a naturally occurring lymphoma from a simian immunodeficiency virus (SIV)-infected rhesus macaque. This analysis revealed rLCV orthologues of the latency-associated EBV circular RNAs circRPMS1_E4_E3a and circEBNA_U.