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[PERSPECTIVES] Bat-Borne Influenza A Viruses: An Awakening
Influenza A viruses (IAVs) originating from aquatic waterfowl recurrently cross interspecies barriers, which is greatly facilitated by utilizing cell surface–exposed monosaccharide sialic acids located on vertebrate cells as a universal host cell receptor. These glycan structures are first bound by the viral hemagglutinin (HA) for cell entry and then cleaved by the viral neuraminidase (NA) for particle release. In contrast, viruses of the recently identified bat-borne IAV subtypes H17N10 and H18N11 encode HA and NA homologs unable to interact with sialic acid residues despite a high degree of structural homology with...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2021 Category: Research Authors: Ciminski, K., Schwemmle, M. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Innate Immunity in Hepatitis C Virus Infection
Activation and viral control of the innate immune response are hallmarks of hepatitis C virus (HCV) infection and are major determinants of spontaneous clearance or progression to chronic infection and liver disease. In this review, we provide a contemporary overview of how HCV is sensed by the host cell to trigger innate immune activation and the mechanisms deployed by the virus to evade this response. Type I and III interferons (IFNs) are crucial mediators of antiviral innate immunity against HCV, and we specifically highlight the importance of IFN- host genetics for the outcome of HCV infection. Last, we focus on the pr...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2021 Category: Research Authors: Schwerk, J., Negash, A., Savan, R., Gale, M. Tags: Hepatitis C Virus: The Story of a Scientific and Therapeutic Revolution PERSPECTIVES Source Type: research

[PERSPECTIVES] Chronic Lymphocytic Leukemia
Patients with chronic lymphocytic leukemia can be divided into three categories: those who are minimally affected by the problem, often never requiring therapy; those that initially follow an indolent course but subsequently progress and require therapy; and those that from the point of diagnosis exhibit an aggressive disease necessitating treatment. Likewise, such patients pass through three phases: development of the disease, diagnosis, and need for therapy. Finally, the leukemic clones of all patients appear to require continuous input from the exterior, most often through membrane receptors, to allow them to survive an...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2021 Category: Research Authors: Chiorazzi, N., Chen, S.-S., Rai, K. R. Tags: Leukemia and Lymphoma: Molecular and Therapeutic Insights PERSPECTIVES Source Type: research

[PERSPECTIVES] A Brain on Cannabinoids: The Role of Dopamine Release in Reward Seeking and Addiction
Cannabis sativa, like all known drugs of abuse, leads to increased dopamine activation within the mesolimbic pathway. Consequent dopamine release within terminal regions of the striatum is a powerful mediator of reward and reinforcement and patterned dopamine release is critical for associative learning processes that are fundamentally involved in addiction. The endocannabinoid system modulates dopamine release at multiple sites, and the receptors, endogenous ligands, and synthetic and metabolic enzymes of the endocannabinoid system may provide key targets for pharmacotherapies to treat disorders of motivation including ad...
Source: Cold Spring Harbor perspectives in medicine - January 4, 2021 Category: Research Authors: Peters, K. Z., Oleson, E. B., Cheer, J. F. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] Medications Development for Treatment of Opioid Use Disorder
This review describes methods for preclinical evaluation of candidate medications to treat opioid use disorder (OUD). The review is founded on the propositions that (1) drug self-administration procedures provide the most direct method for assessment of medication effectiveness, (2) procedures that assess choice between opioid and nondrug reinforcers are especially useful, and (3) states of opioid dependence and withdrawal profoundly influence both opioid reinforcement and effects of candidate medications. Effects of opioid medications and vaccines on opioid choice in nondependent and opioid-dependent subjects are reviewed...
Source: Cold Spring Harbor perspectives in medicine - January 4, 2021 Category: Research Authors: Townsend, E. A., Negus, S. S., Banks, M. L. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] Canine and Feline Influenza
Influenza virus infections of carnivores—primarily in dogs and in large and small cats—have been repeatedly observed to be caused by a number of direct spillovers of avian viruses or in infections by human or swine viruses. In addition, there have also been prolonged epizootics of an H3N8 equine influenza virus in dogs starting around 1999, of an H3N2 avian influenza virus in domestic dog populations in Asia and in the United States that started around 2004, and an outbreak of an avian H7N2 influenza virus among cats in an animal shelter in the United States in 2016. The impact of influenza viruses in domestica...
Source: Cold Spring Harbor perspectives in medicine - January 4, 2021 Category: Research Authors: Wasik, B. R., Voorhees, I. E. H., Parrish, C. R. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] The Two Sides of the Same Coin--Influenza Virus and Intracellular Signal Transduction
Cells respond to extracellular agents by activation of intracellular signaling pathways. Viruses can be regarded as such agents, leading to a firework of signaling inside the cell, primarily induced by pathogen-associated molecular patterns (PAMPs) that provoke safeguard mechanisms to defend from the invader. In the constant arms race between pathogen and cellular defense, viruses not only have evolved mechanisms to suppress or misuse supposedly antiviral signaling processes for their own benefit but also actively induce signaling to promote replication. This creates viral dependencies that may be exploited for novel strat...
Source: Cold Spring Harbor perspectives in medicine - January 4, 2021 Category: Research Authors: Ludwig, S., Hrincius, E. R., Boergeling, Y. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Influenza in Children
Influenza poses a significant disease burden on children worldwide, with high rates of hospitalization and substantial morbidity and mortality. Although the clinical presentation of influenza in children has similarities to that seen in adults, there are unique aspects to how children present with infection that are important to recognize. In addition, children play a significant role in viral transmission within communities. Growing evidence supports the idea that early influenza infection can uniquely establish lasting immunologic memory, making an understanding of how viral immunity develops in this population critical ...
Source: Cold Spring Harbor perspectives in medicine - January 4, 2021 Category: Research Authors: Nayak, J., Hoy, G., Gordon, A. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] T-Cell Immunity against the Hepatitis C Virus: A Persistent Research Priority in an Era of Highly Effective Therapy
Approximately 70% of acute hepatitis C virus (HCV) infections become chronic, indicating that the virus is exceptionally well adapted to persist in humans with otherwise normal immune function. Robust, lifelong replication of this small RNA virus does not require a generalized failure of immunity. HCV effectively subverts innate and adaptive host defenses while leaving immunity against other viruses intact. Here, the role of CD4+ and CD8+ T-cell responses in control of HCV infection and their failure to prevent virus persistence in most individuals are reviewed. Two issues of practical importance remain priorities in an er...
Source: Cold Spring Harbor perspectives in medicine - January 4, 2021 Category: Research Authors: Smith, S., Honegger, J. R., Walker, C. Tags: Hepatitis C Virus: The Story of a Scientific and Therapeutic Revolution PERSPECTIVES Source Type: research

[PERSPECTIVES] HCV Assembly and Egress via Modifications in Host Lipid Metabolic Systems
Hepatitis C virus (HCV) proliferates by hijacking the host lipid machinery. In vitro replication systems revealed many aspects of the virus life cycle; in particular, viral utilization of host lipid metabolism during HCV proliferation. HCV interacts with lipid droplets (LDs) before starting the process of virus capsid formation at the lipid-rich endoplasmic reticulum (ER) membrane compartment. HCV buds into the ER via lipoprotein assembly and secretion. Exchangeable apolipoproteins, represented by apolipoprotein E (apoE), play pivotal roles in enhancing HCV-specific infectivity. HCV virions are likely to interact with othe...
Source: Cold Spring Harbor perspectives in medicine - January 4, 2021 Category: Research Authors: Shimotohno, K. Tags: Hepatitis C Virus: The Story of a Scientific and Therapeutic Revolution PERSPECTIVES Source Type: research

[TECHNIQUE] Mouse Models of Myeloid Malignancies
Mouse models of human myeloid malignancies support the detailed and focused investigation of selected driver mutations and represent powerful tools in the study of these diseases. Carefully developed murine models can closely recapitulate human myeloid malignancies in vivo, enabling the interrogation of a number of aspects of these diseases including their preclinical course, interactions with the microenvironment, effects of pharmacological agents, and the role of non-cell-autonomous factors, as well as the synergy between co-occurring mutations. Importantly, advances in gene-editing technologies, particularly CRISPR&ndas...
Source: Cold Spring Harbor perspectives in medicine - January 4, 2021 Category: Research Authors: Basheer, F., Vassiliou, G. Tags: Leukemia and Lymphoma: Molecular and Therapeutic Insights TECHNIQUE Source Type: research

[PERSPECTIVES] Growth Factors and Alcohol Use Disorder
Neurotrophic growth factors were originally characterized for their support in neuronal differentiation, outgrowth, and survival during development. However, it has been acknowledged that they also play a vital role in the adult brain. Abnormalities in growth factors have been implicated in a variety of neurological and psychiatric disorders, including alcohol use disorder (AUD). This work focuses on the interaction between alcohol and growth factors. We review literature suggesting that several growth factors play a unique role in the regulation of alcohol consumption, and that breakdown in these growth factor systems is ...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Liran, M., Rahamim, N., Ron, D., Barak, S. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] Psychostimulant-Induced Adaptations in Nucleus Accumbens Glutamatergic Transmission
Carrying different aspects of emotional and motivational signals, glutamatergic synaptic projections from multiple limbic and paralimbic brain regions converge to the nucleus accumbens (NAc), in which these arousing signals are processed and prioritized for behavioral output. In animal models of drug addiction, some key drug-induced alterations at NAc glutamatergic synapses underlie important cellular and circuit mechanisms that promote subsequent drug taking, seeking, and relapse. With the focus of cocaine, we review changes at NAc glutamatergic synapses that occur after different drug procedures and abstinence durations,...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Wright, W. J., Dong, Y. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] Influenza in High-Risk Hosts--Lessons Learned from Animal Models
Factoring significantly into the global burden of influenza disease are high-risk populations that suffer the bulk of infections. Classically, the very young, very old, and pregnant women have been identified as high-risk populations; however, recent research has uncovered several other conditions that contribute to severe infection. By using varied animal models, researchers have identified molecular mechanisms underpinning the increased likelihood for infection due to obesity and malnourishment, as well as insight into the role sex hormones play in antiviral immunity in males, in females, and across the life span. Additi...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Honce, R., Wohlgemuth, N., Meliopoulos, V. A., Short, K. R., Schultz-Cherry, S. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[TECHNIQUE] Experimental Approaches to Identify Host Factors Important for Influenza Virus
An ever-expanding toolkit of experimental methods provides the means to discover and characterize host factors important for influenza virus. Here, we describe common methods for investigating genetic relationships and physical interactions between virus and host. A comprehensive knowledge of host:virus interactions is key to understanding how influenza virus exploits the host cell and to potentially identify vulnerabilities that may be manipulated to prevent or treat disease. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Schaack, G. A., Mehle, A. Tags: Influenza: The Cutting Edge TECHNIQUE Source Type: research