Genital HSV-2 Infection Induces Short-Term NK Cell Memory

NK cells are known as innate immune cells that lack immunological memory. Recently, it has been shown that NK cells remember encounters with chemical haptens that induce contact hypersensitivity and cytomegalovirus infection. Here, we show the existence of NK cell memory following HSV-2 infection. Stimulation with HSV-2 Ags led to higher IFNγ production in NK cells that were exposed 30 days previously to HSV-2, compared to NK cells from naïve mice. More importantly, this increased production of IFNγ in NK cells was independent of B- and T- lymphocytes and specific for the HSV-2 Ags. We also showed that previously exposed NK cells in a B- and T-lymphocyte free environment mediate protection against HSV-2 infection and they are necessary for the protection of mice against HSV-2 infection. Collectively, NK cells remember prior HSV-2 encounters independent of B- and T- lymphocytes leading to protection against HSV-2 mediated morbidity and mortality upon re-exposure

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

Lymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans). With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV) is a prevalent α-herpesvirus of poultry, inducing CD4+ TCRαβ+ T cell tumors in susceptible hosts. The high penetrance and temporal predictability of tumor induction raises issues related to the clonal structure of these lymphomas. Similarly, the clonality of responding CD8 T cells that infiltrate the tumor sites is unknown. Using TCRβ repertoire analysis tools, we demonstrated that MDV driven CD4+ T cell tumors were dominated by one to three large clones within an oligoclonal framework of smaller clones of CD4+ T cells. Individual birds had multiple tumor sites, some the result of metastasis (i.e. shared dominant clones) and others derived from distinct clones of transformed cells. The smaller oligoclonal CD4+ cells may represent an anti-tumor response, although on one occasion a low frequency clone was transformed and expanded after culture. Metastatic tumor clones were detected in the blood early during infection and dominated the circulating T cell repertoire, leading to MDV associated immune suppression. We also demonstrated that the tumor-infiltrating CD8+ T cell response was dominated by large oligoclonal expansions containing both “public” and “private” CDR3 sequences. The frequency of CD8+ T cell CDR3 sequences suggests initial stimulation during the early phases of infection. Collectively, our results indicate that MDV driven tumors are dominated by a highly restricted number of CD4+ clones. Moreover, the responding CD8+ T cell infiltrate is oligoclonal indicating recognition of a limited number of MDV antigens. These studies improve our understanding of the biology of MDV, an important poultry pathogen and a natural infection model of virus-induced tumor formation

Gene expression analysis of host spleen responses to Marek's disease virus infection at late tumor transformation phase

Marek\u27s disease is a viral neoplastic disease of chickens caused by Marek\u27s disease virus (MDV). Gene expression patterns have been investigated at different MDV infection stages, but there is limited research about the late tumor transformation phase. In this experiment, 44K Agilent chicken genome-wide expression microarrays were used to profile differential expression in tumorous spleens (TS) from severely morbid chickens and apparently normal spleens from survivors (SS) after MDV infection and expression in noninfected spleens (NS) from controls. There were 4,317 differentially expressed (DE) genes in TS versus NS. However, no DE genes were detected in SS versus NS, suggesting that maintenance of, or return to, homeostasis of gene activity in survivor spleens. Downregulated genes in tumorous spleens mainly enriched in the cytokine-cytokine receptor interaction pathway, and commonly investigated genes in Marek\u27s disease study, IL6, IL18, IFNA, and IFNG were nondifferentially expressed, which indicates host inflammatory response was impaired. The IL10 and TNFRSF8 genes were upregulated in tumorous spleens. We speculated that IL10 might be exploited by MDV to escape from host immune surveillance, as reported for Epstein-Barr virus, which stimulated T cells secreting IL10 to subvert immune response. Previous study reported that transcription from TNFRSF8 promoter could be enhanced by MDV oncogene Meq. In this study, the increased expression of TNFRSF8 indicated interaction between MDV and TNFRSF8, which might facilitate pathogenesis and tumor transformation. The expression of many members in IGF system was changed in tumorous compared with noninfected spleens. The downregulation of IGFBP7 was considered to be associated with MD lymphoma transformation. Gene expression change of multiple regulatory pathways indicated their involvements in facilitating tumor transformation

Seawater zinc/polypyrrole-air cell possessing multifunctional charge-discharge characteristics

An environmentally friendly cell using polypyrrole-air regenerative cathode and zinc as anode is investigated in the 3% sodium chloride solution. The cell can operate in different charge and discharge mode. Polypyrrole can be reoxidized (doped) with chloride anions either by using dissolved oxygen or by an external power supply, e.g., small photovoltaic cell. In that way, after discharge, capacity retaining can be achieved by using seawater as the electrolyte. During low discharge rate, the delicate balance between solid state diffusion-controlled dedoping and chemical oxidation of polypyrrole produced by hydrogen peroxide is achieved, generating stable voltage plateau. The cell is proposed to operate as a power supply for different sensor devices in two modes. In the low discharge mode (10-20 mA g(-1)), it can be used for data acquisition, and at the fast discharge mode (up to 2 A g(-1)) for collecting data transmission

Potential mediators of in ovo delivered double stranded (ds) RNA-induced innate response against low pathogenic avian influenza virus infection

Abstract Background Toll like receptor (TLR) 3 is a critically important innate pattern recognizing receptor that senses many viral infections. Although, it has been shown that double stranded (ds) RNA can be used for the stimulation of TLR3 signaling pathway in a number of host-viral infection models, it’s effectiveness as an antiviral agent against low pathogenic avian influenza virus (LPAIV) needs further investigation. Methods In this study, first, we delivered TLR3 ligand, dsRNA, in ovo at embryo day (ED)18 since in ovo route is routinely used for vaccination against poultry viral and parasitic infections and infected with H4N6 LPAIV 24-h post-treatment. A subset of in ovo dsRNA treated and control groups were observed for the expressions of TLR3 and type I interferon (IFN)s, mRNA expression of interleukin (IL)-1β and macrophage recruitment coinciding with the time of H4N6 LPAIV infection (24 h post-treatment). Additionally, Day 1 chickens were given dsRNA intra-tracheally along with a control group and a subset of chickens were infected with H4N6 LPAIV 24-h post-treatment whereas the rest of the animals were observed for macrophage and type 1 IFN responses coinciding with the time of viral infection. Results Our results demonstrate that the pre-hatch treatment of eggs with dsRNA reduces H4N6 replication in lungs. Further studies revealed that in ovo delivery of dsRNA increases TLR3 expression, type I IFN production and number of macrophages in addition to mRNA expression of IL-1β in lung 24-h post-treatment. The same level of induction of innate response was not evident in the spleen. Moreover, we discovered that dsRNA elicits antiviral response against LPAIV correlating with type I IFN activity in macrophages in vitro. Post-hatch, we found no difference in H4N6 LPAIV genome loads between dsRNA treated and control chickens although we observed higher macrophage recruitment and IFN-β response coinciding with the time of viral infection. Conclusions Our findings imply that the TLR3 ligand, dsRNA has antiviral activity in ovo and in vitro but not in chickens post-hatch and dsRNA-mediated innate host response is characterized by macrophage recruitment and expressions of TLR3 and type 1 IFNs