Yes / Coronavirus is the most dangerous virus in the world wide and it can easy spread between people, animals and plants because it is existing on one strand of RNA (Ribonucleic Acid) and it can duplicate faster than any virus. The source of coronavirus is still unknown, but some sources said that it came from seafood market and other sources said that it came from bat and snakes. It starts in Wuhan; China and every day the fatality increases. The symptoms are like a SARS-CoV (acute respiratory syndrome coronavirus)) and MERS-CoV (Middle East Respiratory Syndrome Coronavirus). By using nucleotide sequence of coronavirus from NCBI (National Center for Biotechnology Information) and some programs that ran on Matlab, the results show that there are some differences and similarities between coronavirus and other viruses such as Ebola, Flu-b, Hepatitis B, HIV and Zika especially for DEBs (distinct excluded blocks) program that shows at 5bp (base pair) there is a common with slightly difference between coronavirus “cgggg” and Ebola virus “cgtgg”. The aim from this study is to find a way to help doctors and scientists to stop spreading the coronavirus or to destroy it.

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 144-172).

Soybean mosaic virus (SMV; Genus Potyvirus; Family Potyviridae) is one of the most widespread viruses in soybean (Glycine max [L.] Merr.). Hutcheson, a cultivar developed in Virginia, is resistant to the common strains of SMV. However, new resistance-breaking (RB) isolates of SMV have emerged in natural infections to break the resistance of Hutcheson containing the Rsv1y allele. These RB isolates are SMV-G5 and G6-like based on the differential reactions on soybean cultivars with the Rsv1 locus, and are more G6-like based on the amino acid sequence of the coat protein (CP). The CP of the RB isolates is diverse at the amino and carboxy termini and highly conserved in the core region. RB isolates reduce the yield of susceptible cultivars and cause mottling of the seed coat. Dual infection of soybeans with SMV and BPMV increased the severity of symptoms, including plant stunting and SMV titer in comparison to single SMV inoculations. The reactions of Hutcheson and herbicide-tolerant Hutcheson RR were similar with or without herbicide application. Resistance to SMV is controlled by single dominant genes at three distinct loci, Rsv1, Rsv3 and Rsv4. The mechanisms of resistance at the Rsv3 and Rsv4 loci were investigated by tracking virus accumulation and movement over time using leaf immunoprints. The mechanisms of Rsv3 resistance include extreme resistance, hypersensitive response, or restriction to virus replication and movement, which are strain specific. The Rsv4 gene was found to function in a non-strain specific and non-necrotic manner. The mechanisms of Rsv4 resistance involve restricting both cell-to-cell and long distance movement of SMV. The Rsv1, Rsv3 and Rsv4 resistance genes exhibit a continuum of SMV-soybean interactions, and include complete susceptibility, local and systemic necrosis, restriction of virus movement (both cell-to-cell and long distance), reduction in virus accumulation, and extreme resistance with no detectable virus. Cultivars containing two genes for resistance, Rsv1 and Rsv3 or Rsv1 and Rsv4, were resistant to multiple strains of SMV tested and show great potential for gene pyramiding efforts to ensure a wider and more durable resistance to SMV in soybeans. / Ph. D.

L'avènement de la trithérapie dès le milieu des années 90 combinées aux mesures de prévention a permis de minimiser les nouvelles contaminations au VIH-1 en plus de reconsidérer l'infection comme une pathologie chronique n'engageant plus le pronostic vital. Cependant, de nombreuses contraintes persistent; la méconnaissance du statut sérologique et l'accès limité ou inexistant à la médication et à la prévention pour certaines populations engendrent encore plus d'un million de nouvelles contaminations et autant de morts chaque année. En outre, les effets secondaires des traitements ainsi que le poids social de vivre avec le virus demeurent problématiques et démontrent la nécessité de poursuivre les efforts de recherche vers une guérison totale du VIH-1. Néanmoins, cet objectif est encore hors de notre portée. En effet, et ce malgré une charge virale indétectable, l'arrêt des traitements entraîne inexorablement une reprise de la propagation virale. La persistance du VIH-1 serait la conséquence de l'établissement précoce de réservoirs viraux anatomiques et cellulaires dans lesquels le virus se réplique à bas bruit ou demeure dans un état latent. Cette latence cellulaire est caractérisée par une présence du génome viral intégré au génome cellulaire, mais ne produisant pas de particules virales. Cette particularité confère aux cellules dites latentes une protection face aux effets toxiques associés à la production virale, ainsi qu'un moyen d'échapper à leur propre élimination parle système immunitaire de l'hôte. Dotées d'une longue durée de vie, ces cellules latentes sont considérées comme les principaux responsables de la reprise de l'infection lors de l'arrêt de la médication. La réactivation de la production virale des cellules latentes permettrait, en théorie, de lever leurs protections menant ainsi à leur élimination. Appelée "shock and kill", cette stratégie, combinée aux traitements pour limiter la propagation virale, représente un atout majeur dans l'éradication du VIH-1. Afin de réactiver la production virale dans les cellules latentes, de nombreuses molécules dénommées agents réactivateurs de la latence (LRA) sont à l'étude depuis plus d'une décennie. Cependant, les agents actuellement étudiés sont non discriminants et l'étude de leurs impacts sont majoritairement limités à la population de lymphocytes T CD4⁺, première population cellulaire identifiée comme infectée de façon latente. L'implication d'autres sous-populations cellulaires, dont notamment les macrophages, dans l'établissement et la progression de l'infection est pourtant avérée. En effet, il est admis que ces cellules contribuent à la formation des réservoirs viraux, la latence virale y étant fortement soupçonnée. La problématique des effets des LRA sur cette sous population cellulaire est ainsi cruciale. Les travaux présentés dans cette thèse visent à étudier l'impact de 3 classes différentes de LRA sur la physiologie des macrophages, leur sensibilité à l'infection par le VIH-1 et leur production virale. Nos résultats ont montré que le traitement des macrophages primaires humains avec certains LRA n'est pas toxique, mais que ces agents sont à même de moduler le transcriptome et le sécrétome de ces cellules. La bryostatine-1, un activateur de la voie PKC, est par exemple associée à des augmentations importantes de médiateurs pro-inflammatoires tels CCL2, CCL5, l'IL-8 et le TNF. Les autres LRA testés induisent des modulations mineures de ces médiateurs alors que cette sécrétion est absente chez les lymphocytes T CD4⁺. De plus, les effets des LRA sur les fonctions physiologiques des macrophages sont minimes, à l'exception d'une diminution de l'efferocytose pour la romidepsine et de l'endocytose dépendante de la transferrine pour la bryostatine-1. La stimulation des macrophages avec les deux molécules précédentes diminue fortement l'expression des récepteurs de surface CCR5 et CD4. Ces modulations sont associées à la diminution de l'infection des macrophages parle VIH-1 sous la dépendance de la modulation de CD4 pour la bryostatine-1 et par l'augmentation de l'activité antivirale de SAMHD1 pour la romidepsine. Le traitement des macrophages infectés aux LRA n'entraîne pas d'augmentation de la transcription ou de la production virale. Néanmoins et de façon surprenante, la bryostatine-1 est associée à une diminution importante de la détection des protéines matures du gène viral codant pour gag sans modulation de leurs précurseurs, et ce, uniquement dans les cellules myéloïdes. Cette étude suggère ainsi que l'impact des LRA diffère selon le type cellulaire, démontrant la nécessité d'étudier les différentes cibles du virus lors des stratégies de cures. / The advent of cART in the mid-1990s combined with preventive measures made it possible to minimize new HIV-1 infections and to reconsider this infection as a chronic no longer life-threatening pathology. However, the constraints remain numerous; the ignorance of the serological status and the limited or nonexistent access to medication and prevention for certain population generates even more than a million of new infections and deaths each year. In addition, the side effects of the treatments and the social burden of living with the virus remain problematic and demonstrate the need to continue research efforts towards a complete cure for HIV-1. However, this concept is still beyond our reach. Indeed, despite an undetectable viral load, treatment interruption ultimately leads to a rebound of viral spread. HIV-1 persistence is believed to be the result of the early establishment of anatomical and cellular viral reservoirs in which the virus replicates at low noise or remains in a latent state. This HIV-1 latency is characterized by an integration of the viral genome into the cell genome without production of viral particles. This peculiarity gives so-called latent cells protection against the toxic effects associated with viral production as well as escaping elimination by the host's immune system. With a long lifespan, these latent cells are considered to be the main culprit in the resumption of infection after medication's termination. The reactivation of the viral production of these latent cells would, in theory, make it possible to lift their protections thus leading to their elimination. Called "shock and kill", this strategy, combined with therapeutic treatments to limit viral spread, represents a major asset in the eradication of HIV-1. To reactivate viral production in latent cells, many molecules known as latency-reversing agents (LRAs) have been under study for more than a decade. However, agents currently studied are non-discriminating and their impacts is mainly limited to the population of CD4⁺ T cells, the first cell population identified as latently infected. Yet, the involvement of many cell populations, including macrophages, in the establishment and progression of the infection is acknowledged. In addition, these cells participate to the HIV-1 reservoirs establishment and are highly suspected to harbor latency. Thus, the problematic of LRAs' effect on this cell population arises. The work presented in this thesis aims to monitor the impact of 3 different classes of LRAs on the physiology of macrophages, their susceptibility to HIV-1 infection and their viral production. Our results have shown that the treatment of primary human macrophages with some LRAs are not toxic but are able to modulate the transcriptome and secretome of these cells. Bryostatin-1, an activator of the PKC pathway, is for example associated with significant increases in proinflammatory mediators such as CCL2, CCL5, IL-8 and TNF. The other LRAs tested induce minor modulations of these mediators while this secretion is absent in CD4⁺ T lymphocytes. Moreover, physiologic features were mostly unchanged by treatment with the studied LRAs except for a downregulation of efferocytosis for romidepsin and transferrin dependent endocytosis for bryostatin-1. Treatment of macrophages with these agents reduces the surface expression of CD4 and CCR5 receptors on macrophages. These modulations were associated with an impairment in HIV-1 infection which relies on CD4 downregulation for bryostatin-1 and SAMHD1 antiviral activity upregulation for romidepsin. Treatment of HIV-1-infected macrophages with LRAs does not increase neither transcription nor viral production. However, and surprisingly, bryostatin-1 is associated with a significant decrease in the production of mature Gag proteins while their precursor level remained unchanged, a mechanism which seemed specific to the myeloid cell lineage. Hence, this study suggests that the impact of LRAs differ depending on the cell type, emphasizing the need to study the different targets of the virus during treatment strategies.

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

No description available.

Primary Epstein-Barr virus (EBV) infection in childhood is typically asymptomatic, but infection later in life results in a mononucleosis with the illness severity ranging from asymptomatic to requiring hospitalisation. The illness is generally short-lived (four to six weeks following onset of symptoms), but persistent disabling symptoms (lasting up to 6 months or longer) are well described in around ten percent of individuals. The aim of this work was to characterise immunological and virological parameters in the peripheral blood, which correlate with persistence of symptoms following EBV-induced mononucleosis. Subjects were recruited prospectively following confirmed primary EBV infection, to allow blood samples and clinical data to be collected at multiple timepoints (baseline, 2 weeks, 4 weeks, 3 months and at least 12 months later). Subjects with 6 months or more of disabling symptoms were defined as ???cases??? with control subjects being those whose illness resolved within 6 weeks of enrolment. Cases were compared with control subjects in terms of: cellular EBV viral load in the peripheral blood by PCR; development of antibodies against EBV VCA (IgG and IgM) and EBNA-1 (IgG) by ELISA; proportions of peripheral blood leucocyte subsets and their activation status by flow cytometry; the magnitude, kinetics of development, and breadth of the CD8+ cytotoxic cell response by interferon-?? Elispot; cytokine levels in serum, and production by peripheral blood mononuclear cells ex vivo; and gene expression patterns in peripheral blood mononuclear cells by microarray. With the exception of gene expression, none of these parameters correlated with early resolution of symptoms or predicted clinical outcome following primary EBV infection. Antibody patterns suggest a tendency to Th2 type immune response may be associated with persistent illness. Preliminary analysis of the gene expression studies indicates that there are many genes involved in this complex disease requiring further investigation. Persistent illness following EBV infection is not associated with uncontrolled viral replication, or chronic immune activation due to an aberrant primary immune response.

The viral dynamics of the hepatitis C virus (HCV) in newly acquired infection are not well understood. HCV exists within an individual as a spectrum of minor variants termed quasispecies. The evolution of minor variants may contribute to viral escape of the host?s immune response, thereby facilitating development of chronic infection. The hypervariable 1 region (HVR1) is the most heterogeneous part of the HCV genome and contains a putative B-cell epitope. Thus, diversity in HVR1 could be a strategy used to evade neutralising antibodies. Acutely infected individuals (n=24) were examined with the aim of defining HVR1 quasispecies diversity in acute infection. The characterisation of the E1/HVR1 sequence and host specific evolution of HCV minor variants in treatment nonresponders was also investigated. HCV E1/HVR1 fragments were amplified from 48 sera using a combined reverse transcription-polymerase chain reaction (RT-PCR). Products were TA cloned into pCRIITOPO and approximately 10-20 clones were sequenced from each sample. HVR1 quasispecies diversity was examined longitudinally via sequence analysis. Quasispecies diversity was characterised primarily by mean nucleotide diversity. The mean HVR1 diversity of the acute cohort (n=48; 2.12% ?? 2.22) was lower than the diversity obtained for a cohort of chronically infected individuals (n=99; 4.5% ?? 5.1). There was no significant difference in mean HVR1 diversity between the HIV/HCV co-infected and HCV mono-infected groups (p=0.99) or between the clearer and non-clearer groups (p=0.85). Examination of amino acid usage and the hydropathic profile of each position in HVR1 revealed that sequence variation was confined to specific sites. The investigation of host specific evolution of HVR1 quasispecies demonstrated that minor variants (comprising 10- 20% of a population) became the dominant species over time in two treatment non-responders. These variants bore mutations that were not reflected in the consensus sequence of their respective populations at the initial timepoint analysed. Common infection was identified by 98% HVR1 sequence homology within two pairs of individuals. The evolution of common strains appeared to be different between individuals, suggesting host pressures may influence quasispecies evolution. This thesis provided an insight into the viral dynamics and host specific evolution of acute phase quasispecies.

The mortality of grouper larvae and juveniles infected by nervous necrosis virus (DGNNV) was near 100%. Vacuoles were found in photoreceptor layer, outer nuclear layer and inner nuclear layer of retina and optic tectum of mesencephalon for the dragon grouper that was infected by DGNNV, after stained with haematoxylin and eosin (H&E). Recombinantly expressed in E. coli, virus-like particles (VLPs) were used for antibody preparation. By indirect fluorescence antibody test (IFAT) with the mouse anti-VLP serum, DGNNV was detected in retina inner nuclear layer and mesencephalon optic tectum. At 96 hours post infection of DGNNV with intraocular injection, vacuoles were observed, with H&E staining, in zebrafish retina photoreceptor layer and mesencephalon optic tectum. In IFAT test, DGNNV was also detected in outer nuclear layer and optic tectum of zebrafish. This study showed antibody stimulated by the recombinant VLPs was sutible for DGNNV detection in fish nervous tissues.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 174-194). Also available online.