Buying Time—The Immune System Determinants of the Incubation Period to Respiratory Viruses

Respiratory viruses cause disease in humans characterized by an abrupt onset of symptoms. Studies in humans and animal models have shown that symptoms are not immediate and appear days or even weeks after infection. Since the initial symptoms are a manifestation of virus recognition by elements of the innate immune response, early virus replication must go largely undetected. The interval between infection and the emergence of symptoms is called the incubation period and is widely used as a clinical score. While incubation periods have been described for many virus infections the underlying mechanism for this asymptomatic phase has not been comprehensively documented. Here we review studies of the interaction between human pathogenic respiratory RNA viruses and the host with a particular emphasis on the mechanisms used by viruses to inhibit immunity. We discuss the concept of the “stealth phase”, defined as the time between infection and the earliest detectable inflammatory response. We propose that the “stealth phase” phenomenon is primarily responsible for the suppression of symptoms during the incubation period and results from viral antagonism that inhibits major pathways of the innate immune system allowing an extended time of unhindered virus replication

The Use of Tail as a Minimal-Invasive Method to Detect a Large Set of Biochemical Responses in the Italian Wall Lizard Podarcis siculus (Rafinesque, 1810)

Conventional methods to analyze biochemical processes related to contaminant toxicity usually require the sacrifice of animals to collect tissues and organs. However, for ethical reasons and especially for endangered species, non- or minimal-invasive methods should be preferred. Among vertebrates, reptiles show a general decline worldwide and therefore the use of non- or minimal-invasive methods to measure some biochemical processes in these animals are encouraged. It is well known that most lizards use a common safety behavior implying the natural loss of tail in the case of predation events. Therefore, if common analyses testing contaminant toxicity could be performed in tail tissue, this method, not implying the sacrifice of the animals, could be considered as a good minimal-invasive method. The aim of this study is to test on wild Italian wall lizard Podarcis siculus the use of tail to detect a large set of biomarkers including oxidative stress (TOSCAROO, TOSCAOH, CAT, tGSH, MDA), biotransformation processes (EROD, GSTs) and neurotoxicity (AChE, BChE). All the biochemical responses, excluding EROD and MDA, resulted to be analytically detectable in tail tissues of P. siculus, although the mean values obtained with this minimal-invasive method were significantly lower than those obtained with invasive one

Global protein sustainability and the United Nations, through to the 2030 agenda

Organizations and initiatives concerned with food security and nutrition have long positioned protein, together with dietary energy, as the keystone for life itself. Indeed, the word protein, derived from the Greek proteios, means ‘of primary importance’. There is a long history of attention to, and controversies over, proteins in UN processes, beginning in the 1930s and continuing to this day. The importance of protein for agriculture, health, food security and nutrition is reflected in the data collected and presented in the statistical databases of the Food and Agriculture Organization (FAOSTAT), available per commodity, per country and over an extensive time series. Protein features directly and indirectly in all 17 Sustainable Development Goals (SDG), which constitute the United Nations 2030 Agenda. Most directly involved is SDG 2. The short title for SDG 2 is ‘zero hunger’. The long title offers more detail: end hunger, achieve food security and improved nutrition and promote sustainable agriculture.fals

Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection. However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response.National Institutes of Health (U.S.

Endogenous antigen processing drives the primary CD4+ T cell response to influenza.

By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with major histocompatibility complex class II molecules. Alternative pathways of epitope production have been identified, but their contributions to host defense have not been established. We show here in a mouse infection model that the CD4+ T cell response to influenza, critical for durable protection from the virus, is driven principally by unconventional processing of antigen synthesized within the infected antigen-presenting cell, not by classical processing of endocytosed virions or material from infected cells. Investigation of the cellular components involved, including the H2-M molecular chaperone, the proteasome and γ-interferon-inducible lysosomal thiol reductase revealed considerable heterogeneity in the generation of individual epitopes, an arrangement that ensures peptide diversity and broad CD4+ T cell engagement. These results could fundamentally revise strategies for rational vaccine design and may lead to key insights into the induction of autoimmune and anti-tumor responses

The effector T cell response to influenza infection

Influenza virus infection induces a potent initial innate immune response, which serves to limit the extent of viral replication and virus spread. However, efficient (and eventual) viral clearance within the respiratory tract requires the subsequent activation, rapid proliferation, recruitment, and expression of effector activities by the adaptive immune system, consisting of antibody producing B cells and influenza-specific T lymphocytes with diverse functions. The ensuing effector activities of these T lymphocytes ultimately determine (along with antibodies) the capacity of the host to eliminate the viruses and the extent of tissue damage. In this review, we describe this effector T cell response to influenza virus infection. Based on information largely obtained in experimental settings (i.e., murine models), we will illustrate the factors regulating the induction of adaptive immune T cell responses to influenza, the effector activities displayed by these activated T cells, the mechanisms underlying the expression of these effector mechanisms, and the control of the activation/differentiation of these T cells, in situ, in the infected lungs

Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine

Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205–targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-γ– and interleukin 2–producing CD4+ T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4+ and IFN-γ–dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4+ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities

USE OF CAGED MUSSEL MYTILUS GALLOPROVINCIALIS IN AN ECOTOXICOLOGICAL APPROACH TO ASSESS ENVIRONMENTAL IMPACT IN OFF-SHORE ACTIVITIES

Abstract Mediterranean mussels, Mytilus galloprovincialis, are well recognized bioindicator organisms which can be easily caged in investigated areas to assess the impact of anthropogenic activities. In this work a monitoring protocol was developed for off-shore installations in the Adriatic sea. Integration of chemical analyses with a wide range of biomarkers analysed in mussels caged at 2 platforms, allowed to evaluate the biological disturbance and confirmed the utility of the ecotoxicological approach for monitoring off-shore activities. Keywords : Bio-indicators, Adriatic Sea. Several environmental issues are associated with the off-shore oil and gas industry, from the impact caused during installation to various form of disturbance related to daily ship traffic, extraction activities, maintenance of structures and, finally, decommissioning of old platforms. During the last year a monitoring protocol with caged mussels, Mytilus galloprovincialis, has been developed, to evaluate the potential ecotoxicological effects caused from the off-shore platform "Giovanna" in the Adriatic sea. Obtained results allowed to exclude marked biological disturbance and demonstrated the suitability of this approach. In this respect considering "Giovanna" as model platform, the monitoring protocol with caged mussel has been extended including also another off-shore installation, the "Emilio" platform. In this work native mussels were collected on a seasonal basis from a reference site on the Adriatic coast (Portonovo, Ancona) and transplanted for 4-6 weeks in both the sampling area and to the investigated platform "Giovanna" (42 • 46' 060N, 14 • 27' 750E) and Emilio (42 • 56' 305 N; 14 • 13' 915 E). After the translocation period, mussels were recovered dissected tissues frozen in liquid nitrogen and maintained at -80 • C until analyses. Chemical analyses on trace metals (arsenic, cadmium, chromium, copper, iron, mercury, manganese, nickel, lead, zinc) in mussels tissues An overall evaluation of results confirmed the absence of marked biological effects caused by the activities of "Giovanna" platform, as already demonstrated during the previous monitoring project. More variations were observed in mussels translocated to "Emilio", i.e. higher activities of glutathione S-transferases, catalase and peroxisomal proliferation decrease of oxyradical scavenging capacity toward hydroxyl and peroxyl radicals and lysosomal destabilization (inhibition of neutral red retention time), indicating an onset of impairment condition in the organisms. Compared to mussels transplanted at the reference site, those from "Emilio" platform did not exhibit more elevated concentrations for the various metals and only for zinc and cadmium an higher bioavailability was detected close to the platform, suggesting the influence of galvanic anodes for cathodic protection. The overall results of this work confirmed the utility of using caged mussels as an additional contribution for monitoring off-shore activities and provided an ecotoxicological protocol based on cellular biomarkers for the early detection of biological disturbance

Experimental rat bladder urothelial cell carcinoma models

Bladder cancer is a major public health problem. Currently available therapeutic options seem to be unable to prevent bladder cancer recurrence and progression. To enable preclinical testing of new intravesical therapeutic agents, a suitable bladder tumor model that resembles human disease is highly desirable. The aim of this topic paper was to discuss the problems associated with current in vivo animal bladder tumor models, focusing on the orthotopic syngeneic rat bladder tumor model. In the second part of the paper the development of a potential new orthotopic rat bladder tumor model is described