Following acute encephalitis, Semliki Forest virus is undetectable in the brain by infectivity assays but functional virus RNA capable of generating infectious virus persists for life

Alphaviruses are mosquito-transmitted RNA viruses which generally cause acute disease including mild febrile illness, rash, arthralgia, myalgia and more severely, encephalitis. In the mouse, peripheral infection with Semliki Forest virus (SFV) results in encephalitis. With non-virulent strains, infectious virus is detectable in the brain, by standard infectivity assays, for around ten days. As we have shown previously, in severe combined immunodeficient (SCID) mice, infectious virus is detectable for months in the brain. Here we show that in MHC-II-/- mice, with no functional CD4 T-cells, infectious virus is also detectable in the brain for long periods. In contrast, in the brains of CD8-/- mice, virus RNA persists but infectious virus is not detectable. In SCID mice infected with SFV, repeated intraperitoneal administration of anti-SFV immune serum rapidly reduced the titer of infectious virus in the brain to undetectable, however virus RNA persisted. Repeated intraperitoneal passive transfer of immune serum resulted in maintenance of brain virus RNA, with no detectable infectious virus, for several weeks. When passive antibody transfer was stopped, antibody levels declined and infectious virus was again detectable in the brain. In aged immunocompetent mice, previously infected with SFV, immunosuppression of antibody responses many months after initial infection also resulted in renewed ability to detect infectious virus in the brain. In summary, antiviral antibodies control and determine whether infectious virus is detectable in the brain but immune responses cannot clear this infection from the brain. Functional virus RNA capable of generating infectious virus persists and if antibody levels decline, infectious virus is again detectable

English for Strufents of Biological Departments

Структура пособия позволяет выбрать оптимальные способы организации работы для эффективного усвоения материала и аналитической обработки информации.Данное пособие предназначено для студентов I курса биологического факультета университета. В пособии представлены оригинальные тексты и упражнения к ним, способствующие закреплению лексического и грамматического материала

Studies on the release of neutrophil extracellular traps and IFN-γ as part of the innate immune response to Aspergillus fumigatus and on the fungal stress response via the hybrid sensor kinase TcsC

Aspergillus fumigatus is a saprophytic mold that naturally inhabits the soil. Asexual reproduction yields hardy conidia that circulate in the air and are inhaled daily by humans. The fungus seems not to have evolved distinct mechanisms of pathogenicity, but is capable of responding to many stressful environmental cues present in its naturally harsh niche. The robust conidia present no problem to a fully functioning immune system, but if the innate immune system is compromised, the conidia can become activated and differentiate within the lung tissue to form invasive and disseminating hyphae. The resulting disease is called aspergillosis and is difficult to detect and to treat. To date, scientists have yet to find the factor(s) missing during immunosuppression that allow a healthy patient to easily dispose of A. fumigatus. We explored two possibilities: the production of neutrophil extracellular traps (NETs) and the release of IFN-γ by natural killer (NK) cells. We report here that NETs alone cannot kill the fungus, but do inhibit polar growth. Elongation of hyphal tips is abrogated due to zinc starvation, likely a consequence of the zinc-chelating, NETs-associated protein calprotectin. NK cells alone are also incapable of fungicidal activity, but their release of IFN-γ upon contact with A. fumigatus abrogates hyphal growth by a yet unknown mechanism. In vitro studies of the innate immune response, though helpful, are far from representative of the in vivo response. Neither NETs nor IFN-γ alone can manage Aspergillus infection, but in combination, these and other immune assaults certainly can. The difficulty lies in identifying the precise combination of immune cells and cytokine milieu that in a healthy individual prevent infection. Additionally, we explored mechanisms by which the fungus responds to stress, namely the HOG MAPK pathway, historically involved in osmotic stress response. In filamentous fungi, certain stress signals are sensed by a cytoplasmic hybrid histidine kinase sensor and then passed through the HOG system via phosphorylation. We identified the putative hybrid sensor kinase in A. fumigatus, and generated a corresponding knockout mutant. The ΔtcsC mutant was indeed sensitive to osmotic stress, and resistant to the phenolpyrrole fungicide fludioxonil. In the wild type the addition of either osmotic stress or fludioxonil resulted in SakA phosphorylation and translocation to the nucleus. SakA, the Hog1 homolog in A. fumigatus, is located at the end of the HOG pathway, confirming the role of TcsC as the cytoplasmic sensor upstream of SakA. In hypoxia, on farnesol, and in high concentrations of divalent cations the ΔtcsC mutant exhibited a striking “fluffy” phenotype characterized by the production of tremendous aerial hyphae and little or no differentiation, i.e., no conidiation. Though the ΔtcsC mutant showed no change in virulence compared to wild type, components of the TcsC signalling pathway remain promising targets for antifungal agents

Selected themes of histology, cytology and embryology core

CYTOLOGYEMBRYOLOGYHISTOLOGYГИСТОЛОГИЯУЧЕБНЫЕ ПОСОБИЯЦИТОЛОГИЯЭМБРИОЛОГИЯThe study manual includes topics on histology, cytology and embryology core

A Novel Methodology for Isolating Broadly Neutralizing HIV-1 Human Monoclonal Antibodies

Abstract also published in AIDS Research and Human Retroviruses. November 2013, 29(11): A-53. doi:10.1089/aid.2013.1500Poster presentationpublished_or_final_versio

Medicine + Health Magazine, Spring 2016

https://hsrc.himmelfarb.gwu.edu/smhs_medhealth/1011/thumbnail.jp

Elicitation of broadly neutralizing HIV-1 antibodies by guiding the immune responses using primary and secondary immunogens

Abstract also published in AIDS Research and Human Retroviruses. November 2013, 29(11): A-44. doi:10.1089/aid.2013.1500Poster presentationpublished_or_final_versio

Global Bioethics

Two new factor have been added to the ideological change in the second half of the past century: the “ecological impact” of humankind on the environment due to the population increase; and the “ innovative impact of science, first with atomic physics, which introduced the scission of the fundamental unit of matter, the atom, and then witch molecular biology, which led to the decoding of genetic information and intervention of biological engineering that annihilate our concepts of individual and species as fundamental units in biology. This stage of fundamental rethinking is however overshadowed by the threat of ecological disaster and catastrophic population increase, which not only impose limits to development, but undermine the very survival of Humankind. The future survival our species in fact depends on the interaction between its reproductive characteristics and the productivity of the territory, which, even if increased by the intellectual capability of the human brain, has intrinsically limits. The adaptive choices (which are also biotechnological and biomedical) of the interaction between human population and the natural ambience is the conceptual basis of the new discipline “Global Bioethics”