Occupational therapy practitioners (OTPs) are negatively affected by a rise in healthcare burnout. Increased job demands (Broiler et al.,1986; Bessolo; 2015; Derakhshanrad et al., 2019; Stephenson, 2019) and the COVID-19 pandemic (Kuhl et al., 2021) have exacerbated work-related stress and burnout in OTPs leading to a decline in creativity (Hickey, 2016; Oven & Lobe, 2019; Derakhshanrad et al., 2019) which may result in decreased quality of care for their clients. The stress and burnout that OTPs experience may have a negative impact on their ability to generate novel ideas and problem-solve (Hickey, 2016). The clinical consequences that result from decreased quality of care are non-client-centered treatments, reduced joy and satisfaction at work, and difficulty maintaining motivation. The proposed intervention is a three-hour webinar, Creativity Leads to Positivity, which educates OTPs on different creative thinking strategies. During the webinar, the 8-P theoretical framework — a creative thinking theory — as well as four creative thinking strategies — the De Bono technique, Synectics, the Creative Problem Solving model, and Design Thinking — will be discussed.

This dissertation is a tale of two emerging human pathogens. The first is a genus of viruses, orthoebolaviruses, which periodically cause outbreaks in humans in central and western Africa following spillover from animal reservoirs. Outbreaks of orthoebolaviruses have high rates of morbidity and mortality and can cause symptoms ranging from vomiting and diarrhea to hemorrhage. Understanding both how the virus evolves to fit its host as well as how the host reacts to viral infection is paramount to understanding what determines whether an infected patient will die or survive orthoebolavirus infection. To understand how orthoebolavirus genomic plasticity allows the virus to optimize itself to its host, I analyzed viral genomic sequencing data from two Orthoebolavirus species during serial passage in tissue culture: Ebola virus and Sudan virus. In low-passage Sudan virus, I discovered a true viral quasispecies in which three to four viral genotypes circulated within the same stock. I then examined how that quasispecies reacted when put into a nonhuman primate model (NHP) of infection; unexpectedly, we saw that the mix of genotypes in the challenge stock matched the mix of genotypes seen at clinical endpoint. To begin to understand what a successful immune response to orthoebolavirus infection entails, I characterized the circulating transcriptomic response in two survival models of Ebola virus disease. In a uniform survival model where NHPs were challenged with Bombali virus, I showed that NHPs have a clear and robust response to infection despite varying symptom severity. In a Taï Forest virus challenge model with ~44% survival, I showed that NHPs that succumb do so in a uniform manner consistent with other models of Ebola virus disease. In contrast, survivors were highly variable in their response to infection: some mimicked the non-survivor response but recovered in time, while others hardly responded at all. After covering orthoebolavirus genomic plasticity and the host response to infection in the first and second sections, respectively, I will then shift to the other focus of my dissertation work: SARS-CoV-2 and molecular epidemiology. SARS-CoV-2 swept the globe in 2020 following spillover into humans from an animal reservoir in late 2019, and surveillance sequencing of viral genomes early in the pandemic showed the virus was rapidly adapting to its new host. I leveraged this high mutation rate to spin up a molecular epidemiology operation for Boston Medical Center (BMC) and Boston University (BU). From mid-2020 through spring 2022, I catalogued, processed, sequenced, and analyzed samples and viral genomes from over 7,000 SARS-CoV-2 patient swabs. I worked with contact tracing teams, physicians, and infection control from BU and BMC to quantify viral introductions, identify transmission chains, and integrate the genetic linkages with traditional epidemiological data. / 2025-01-11T00:00:00Z

The last five years have shown us the profound impact that SARS-CoV-2 pandemic has had on human kind and made us aware of the dangers that emerging pathogens can present. The goal of this dissertation is to use mathematical models in connection with data to uncover mechanistic interactions governing viral infections. To acquire a holistic understanding of the impact of viral infections, it is necessary to develop mathematical techniques and models that bridge knowledge on multiple biological scales. This dissertation explores the relationship between within-host virus dynamics, the environment and the between-host viral transmission. We will validate the models against data from SARS-CoV-2 infections, and data from infections with an emerging pathogen, the Usutu virus. Our models of SARS-CoV-2 infection looked at the relationship between infectious virus and viral RNA in the body and in the environment. Using golden hamster data and within-host mathematical models, we determined that infectious virus shedding early in infection correlates with transmission events, shedding of infectious virus diminishes late in the infection, and high viral RNA levels late in the infection are a poor indicator of transmission. We further showed that viral infectiousness increases in a density dependent manner with viral RNA and that their relative ratio is time-dependent. Such information is useful for designing interventions. Our models of Usutu virus infection looked at differences between different virus strains during bird infections. Within-host models applied to data showed heterogeneity in viral strain dynamics, and correlated high basic reproductive number with short infected cell lifespan (indicative of immune responses) and correlated low basic reproductive number with low viral peaks and longer lasting viremia (due to lower infection rates and high infected cell lifespan). We expanded the models to investigate multiscale dynamics connecting within-host scale, bird-to-vector transmission scale, and vector-borne epidemiological scale. One important direction of this dissertation is the investigation of uncertainty in parameter estimation and overall model identifiability. We conducted identifiability studies (using several theoretical tools) in the multiscale models of Usutu virus infection and in several within-host influenza models. Model identifiability is critical to the reproducibility of modeling results in any biological systems. In this dissertation, we will show how insights from such analyses inform both modeling practices and experimental design. / Doctor of Philosophy / The last five years have shown us the profound impact that SARS-CoV-2 pandemic has had on human kind and made us aware of the dangers that emerging pathogens can present. Within-host mathematical models are tools that can be used to study the dynamics of virus infections. These models help us gain an understanding of biological quantities of interest, relationships between biological processes in a quantitative and qualitative ways, and disease outcome. However, to acquire a holistic understanding of the impact of viral infections, it is necessary to develop mathematical tools and models that bridge knowledge on multiple biological scales. This dissertation explores the relationship between virus infection characteristics over time in a single host and larger biological scales including virus' release into the environment and spread of virus between hosts. Biological and public health insights about SARS-CoV-2 and Usutu virus were gained through these modeling efforts.

No description available.

Mon travail de thèse s’est focalisé sur l’étude fonctionnelle de deux méthyltransférases (MTases) de la structure coiffe des ARNs, les protéines nsp14 et nsp16, chez le coronavirus responsable du syndrome respiratoire du Moyen-Orient (MERS-CoV). Notre étude a démonté un processus de méthylation séquentiel. La coiffe est d’abord méthylée en position N7 par nsp14 formant la coiffe-0 (7mGpppN). La coiffe-0 est ensuite méthylée en position 2’OH du premier nucléotide de l’ARN par nsp16 stimulée par nsp10 formant une coiffe 1 (7mGpppN2’Om). De plus, nos résultats suggèrent un mécanisme de régulation allostérique de l’activité de nsp16 par nsp10. Nos résultats indiquent que l’interaction nsp10/nsp16 est régulée par la variation de concentration du SAM et/ou de SAH. Le SAM présent à une concentration physiologique, environ 100 µM dans les cellules, favorise l’assemblage du complexe nsp10/nsp16. La faible concentration intracellulaire du SAH produit accélère la dissociation du complexe nsp10/nsp16 permettant le « turnover » de la réaction enzymatique. Par ailleurs, nous avons cartographié les résidus essentiels au recrutement de l’ARN par nsp16. Les méthylations étudiées jouent un rôle important dans la réplication virale. Nous avons donc criblé des inhibiteurs des deux MTases nsp14 et nsp10/nsp16 respectivement à partir des chimiothèques « Prestwick » et « 2P2I3D ». En résumé, mon travail de thèse a décortiqué les bases moléculaires de méthylation de la coiffe chez le MERS-CoV et a permis d’identifier des inhibiteurs de MTases représentant un point de départ crucial pour le développement d’antiviraux contre les CoV. / My PhD work focused on the functional study of two cap RNA methyltransferases (MTases), nsp14 and nsp16, of the Middle-East respiratory syndrome coronavirus (MERS-CoV). Our study demonstrates a sequential methylation process. The cap is first methylated at the N7 position by nsp14 forming a cap-0 (7mGpppN). It is next methylated at the 2’OH position of the first transcribed nucleotide by nsp16 stimulated by nsp10 forming a cap-1 (7mGpppN2’Om). Furthermore, our results suggest an allosteric regulation mechanism of the nsp16 activity by nsp10. Moreover, our results indicate that the nsp10/nsp16 interaction is regulated by the variation of SAM and/or SAH concentration. SAM present at physiologic concentration, around 100µM in cells, enhances the assembly of nsp10/nsp16. The weak intracellular concentration of SAH by-product speeds up the dissociation of nsp10/nsp16 allowing the enzymatic reaction turnover. In addition, we have mapped the essential residues for the recruitment of the RNA by nsp16. The methylations studied in this work play an important role for viral replication. We have therefore screened inhibitors of nsp14 and nsp10/nsp16 MTases respectively from chemical libraries « Prestwick » and « 2P2I3D ». In summary, my PhD work deciphers the molecular bases of cap RNA methylation of MERS-CoV and identifies MTase inhibitors that represent a crucial starting point for the development of antivirals against CoV.

Doenças infecciosas emergentes se caracterizam como enfermidades cujos patógenos evoluíram para uma nova cepa ou genótipo capaz de infectar tanto o mesmo hospedeiro quanto uma nova espécie. A ocorrência de doenças emergentes tem sido correlacionada à destruição de habitats e à perda de biodiversidade. As aves marinhas têm sido consideradas bons indicadores e sentinelas do ecossistema aquático, e uma ampla variedade de enfermidades virais têm sido investigadas e descritas em aves no mundo todo. A caracterização e o entendimento das enfermidades virais que acometem as aves marinhas que habitam a costa brasileira são de fundamental importância para a compreensão de possíveis surtos de mortalidade dentre outros fatores que interferem na conservação das aves em geral. O objetivo desta pesquisa foi investigar a ocorrência de herpesvírus, avipoxvírus e coronavírus nas espécies de aves marinhas que foram reabilitadas em três centros localizados ao longo da costa brasileira e nas colônias reprodutivas de Sula sp. e Phaeton sp. localizadas no arquipélago de Abrolhos, Bahia, Brasil, e em quatro colônias de Spheniscus magellanicus localizadas na Patagônia argentina. As análises virais foram realizadas pela técnica de PCR e RT-PCR e confirmadas pela reação de sequenciamento do amplicon identificado. Nos casos de óbito, as alterações histopatológicas foram identificadas por meio de análise microscópica. O estudo revelou a ocorrência dos três agentes virais identificados em centros de reabilitação no Brasil, além da ocorrência de herpesvírus nas populações de vida livre e ativas em seus sítios reprodutivos. Foram identificados quatro novos herpesvírus denominados: Magellanic penguin herpesvirus 1 (MagHV -1) causador de um surto de mortalidade associado a traqueíte necrótico-hemorrágica em pinguins de Magalhães em reabilitação; Magellanic penguin herpesvirus 2 (MagHV-2), identificado em pinguins de Magalhães aparentemente saudáveis nas colônias reprodutivas da Patagônia argentina; Sulid herpesvirus 1 (SuHV -1), identificado em atobás (Sula sp.) e grazinas (Phaeton sp.) nas colônias reprodutivas de Abrolhos e Thalassarchid herpesvirus 1 (ThHV -1), identificados em um albatroz de nariz amarelo (Thalassarche chlororhynchos) nas praias de Rio Grande, RS, Brasil. Também foram identificados: um novo avipox, denominado Brazilian penguinpox, causador de lesões cutâneas, esofágicas e respiratórias nos pinguins de Magalhães cutâneas, esofágicas e respiratórias nos pinguins de Magalhães em reabilitação em Santa Catarina e a identificação de dois Gammacoronavirus em três diferentes espécies assintomáticas que estavam em reabilitação em Santa Catarina e no Rio Grande do Sul. Os dados obtidos constituem uma base de informação útil para estudos futuros no campo da patologia, virologia, epidemiologia e dos impactos antrópicos na saúde das aves marinhas do cone sul. / Emerging infectious diseases are characterized as disease whose pathogens progressed to a new strain ar genotype capable of infecting the same host or a new species. The occurrence of emerging diseases has been correlated to the destruction of habitats and loss of biodiversity. Seabirds have been considered as good indicators and sentinels of aquatic ecosystem, and a wide variety of viral diseases have been investigated and described in birds worldwide. The characterization and understanding of viral diseases that affect seabirds that inhabit the Brazilian coast are of fundamental importance for the understanding of possible mortality outbreaks among other factors that influence the conservation of birds in general. The objective of this research was to investigate the occurrence of herpesvirus, coronavirus and avipoxvirus in seabird species that were rehabilitated in three centres located along the Brazilian coast and in breeding colonies of Sula sp. and Phaeton sp. located at the Abrolhos’s archipelago, Bahia, Brazil and four Spheniscus magellanicus's colonies located at Argentina's Patagonia. Viral analyzes were performed by PCR and RT-PCR and confirmed by sequencing the identified amplicon. In cases of death, the histopathological alterations were identified through optical microscopic analysis. The study revealed the occurrence of the three investigated viral agents in the Brazilian rehabilitation centres, besides the occurrence of herpesvirus in the freeliving and reproductive active seabird’s populations. Four new herpesvirus were identified and called: Magellanic penguin herpesvirus 1 (MagHV -I), causing a mortality outbreak associated with necrotic-hemorrhagic tracheitis in Magellanic penguins in rehabilitation process; Magellanic penguin herpesvirus 2 (MagHV-2), identified in apparently healthy breeding Magellanic penguins at the Argentinean Patagonia’s colonies; Sulid herpesvirus 1 (SuHV-l), identified in boobies (Sula sp.) and tropicalseabirds (Phaeton sp.) breeding colonies at Abrolhos Archipelago, and Thalassarchid herpesvirus 1 (ThHV -1), identified in a yellow nose albatross (Thalassarche chlororhynchos) that appeared on the beaches of Rio Grande, RS, Brazil. Were. also identified: a new avipox named Brazilian penguinpox causing cutaneous, esophagus and respiratory lesions in rehabilitation penguins at Santa Catarina and the identification of two Santa Catarina and the identification of two Gammacoronavirus in three different asymptomatic seabirds species that were undergoing rehabilitation in Santa Catarina and Rio Grande do Sul. The data provi de a useful information basis for further studies related to pathology, virology, epidemiology and human impacts on southern hemispheres seabirds’ health.

3C-like protease (3CLpro) of severe acute respiratory syndrome-coronavirus (SARS-CoV) is required for autoprocessing of the polyproteins 1a and 1ab, and is a potential target for treating coronaviral infection. To obtain a thorough understanding of its substrate preference, we created a substrate library of 19 x 8 variants by performing saturation mutagenesis on the autocleavage sequence at P5 to P3' positions. The substrate sequences were inserted between cyan and yellow fluorescent proteins so that the cleavage rates were monitored by in vitro fluorescence resonance energy transfer (FRET). The relative cleavage rate for different substrate sequences was correlated with various structural properties. P5 and P3 positions prefer residues with high beta-sheet propensity P4 prefers small hydrophobic residues: P2 prefers hydrophobic residues without beta-branch. Gln is the best residue at P1 position, but observable cleavage can be detected with His and Met substitutions. P1' position prefers small residues, while P2' and P3' positions have no strong preference on residue substitutions. Noteworthy, solvent exposed sites such as P5, P3 and P3' positions favour positively charged residues over negatively charged one, suggesting that electrostatic interactions may play a role in catalysis. A super-active substrate, which combined the preferred residues at P5 to P1 positions, was found to have 2.8 fold higher activity than the wild-type sequence. / Inhibition of SARS-CoV 3CLpro proteolytic activity suppresses virion replication and virus-induced cytopathic effects. Peptidomimetic inhibitors with nitrile warheads, which inhibit Cys protease activity, have been applied for clinical therapy. To investigate whether the nitrile group can target 3CLpro, a series of nitrile-based peptidomimetic inhibitors with various protective groups, peptide length and peptide sequences were synthesized. Inhibitor potency in terms of IC50 and Ki values was determined by FRET assay. Most of these nitrile-based inhibitors in micromolar range can significantly reduce 3CLpro activity. The most potent inhibitor is the tetrapeptidomimetie inhibitor linked with carbobenzyloxy (cbz) group 'cbz-AVLQ-CN' with IC50 and Ki values of 5.9 +/- 0.6 muM and 0.62 +/- 0.11 muM respectively. Crystal structures of 3CLpro-inhibitor complexes demonstrated that nitrite warhead covalently bonded to Cys145, while P1 -- P4 residues interacted with 3CLpro as substrate bound. The cbz group in 'cbz-AVLQ-CN' flipped into a cavity of Gu166 -- Pro168, providing an extra binding force to enhance inhibitor potency. In conclusion, the nitrile-based peptidomimetic inhibitor with cbz group is a convincing model for drug development. / Substrate specificities of various 3CLpro were further investigated by using the substrate library of SARS-CoV 3CLpro. Among various viral strains, the proteases of HCoV-NL63, HCoV-OC43 and infectious bronchitis virus (IBV) were selected from group I, IIa and III respectively for specificity profiling. Their proteolytic rates against 19 x 8 variants were obtained by FRET assay, and correlated with structural properties of substituting residues. Like SARS-CoV 3CLpro in group IIb, these 3CLpro consistently prefer small hydrophobic P4 residues, positively charged P3 residues, hydrophobic P2 residues without beta-branch, P1-Gln and small P1' residues. These proteases also tend to accommodate P5 and P3' residues with positive charge, and P2' residues with small size. In contrast, their preferences on secondary structure are diverse. Correlation was found between IBV 3Clpro activity and beta-sheet propensity at P5 position, while no strong correlation with secondary structure propensities was observed in HCoV-NL63 and HCoV-0C43. Collectively, all 3CLpro share universal preferences on charge, side chain volume and hydrophobicity, but not secondary structure. Their relative activities against universal and specific super-active substrates were elevated to 1.4 -- 4.3, showing synergetic effects by combining preferred residues. These substrates were examined by group I HCoV-229E and group IIa HCoV-HKU1 in parallel. Their activities were highly comparable to those of other group members. / Chuck, Chi Pang. / Adviser: Chi-Cheong Wan. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves [179]-187). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Doenças infecciosas emergentes se caracterizam como enfermidades cujos patógenos evoluíram para uma nova cepa ou genótipo capaz de infectar tanto o mesmo hospedeiro quanto uma nova espécie. A ocorrência de doenças emergentes tem sido correlacionada à destruição de habitats e à perda de biodiversidade. As aves marinhas têm sido consideradas bons indicadores e sentinelas do ecossistema aquático, e uma ampla variedade de enfermidades virais têm sido investigadas e descritas em aves no mundo todo. A caracterização e o entendimento das enfermidades virais que acometem as aves marinhas que habitam a costa brasileira são de fundamental importância para a compreensão de possíveis surtos de mortalidade dentre outros fatores que interferem na conservação das aves em geral. O objetivo desta pesquisa foi investigar a ocorrência de herpesvírus, avipoxvírus e coronavírus nas espécies de aves marinhas que foram reabilitadas em três centros localizados ao longo da costa brasileira e nas colônias reprodutivas de Sula sp. e Phaeton sp. localizadas no arquipélago de Abrolhos, Bahia, Brasil, e em quatro colônias de Spheniscus magellanicus localizadas na Patagônia argentina. As análises virais foram realizadas pela técnica de PCR e RT-PCR e confirmadas pela reação de sequenciamento do amplicon identificado. Nos casos de óbito, as alterações histopatológicas foram identificadas por meio de análise microscópica. O estudo revelou a ocorrência dos três agentes virais identificados em centros de reabilitação no Brasil, além da ocorrência de herpesvírus nas populações de vida livre e ativas em seus sítios reprodutivos. Foram identificados quatro novos herpesvírus denominados: Magellanic penguin herpesvirus 1 (MagHV -1) causador de um surto de mortalidade associado a traqueíte necrótico-hemorrágica em pinguins de Magalhães em reabilitação; Magellanic penguin herpesvirus 2 (MagHV-2), identificado em pinguins de Magalhães aparentemente saudáveis nas colônias reprodutivas da Patagônia argentina; Sulid herpesvirus 1 (SuHV -1), identificado em atobás (Sula sp.) e grazinas (Phaeton sp.) nas colônias reprodutivas de Abrolhos e Thalassarchid herpesvirus 1 (ThHV -1), identificados em um albatroz de nariz amarelo (Thalassarche chlororhynchos) nas praias de Rio Grande, RS, Brasil. Também foram identificados: um novo avipox, denominado Brazilian penguinpox, causador de lesões cutâneas, esofágicas e respiratórias nos pinguins de Magalhães cutâneas, esofágicas e respiratórias nos pinguins de Magalhães em reabilitação em Santa Catarina e a identificação de dois Gammacoronavirus em três diferentes espécies assintomáticas que estavam em reabilitação em Santa Catarina e no Rio Grande do Sul. Os dados obtidos constituem uma base de informação útil para estudos futuros no campo da patologia, virologia, epidemiologia e dos impactos antrópicos na saúde das aves marinhas do cone sul. / Emerging infectious diseases are characterized as disease whose pathogens progressed to a new strain ar genotype capable of infecting the same host or a new species. The occurrence of emerging diseases has been correlated to the destruction of habitats and loss of biodiversity. Seabirds have been considered as good indicators and sentinels of aquatic ecosystem, and a wide variety of viral diseases have been investigated and described in birds worldwide. The characterization and understanding of viral diseases that affect seabirds that inhabit the Brazilian coast are of fundamental importance for the understanding of possible mortality outbreaks among other factors that influence the conservation of birds in general. The objective of this research was to investigate the occurrence of herpesvirus, coronavirus and avipoxvirus in seabird species that were rehabilitated in three centres located along the Brazilian coast and in breeding colonies of Sula sp. and Phaeton sp. located at the Abrolhos’s archipelago, Bahia, Brazil and four Spheniscus magellanicus's colonies located at Argentina's Patagonia. Viral analyzes were performed by PCR and RT-PCR and confirmed by sequencing the identified amplicon. In cases of death, the histopathological alterations were identified through optical microscopic analysis. The study revealed the occurrence of the three investigated viral agents in the Brazilian rehabilitation centres, besides the occurrence of herpesvirus in the freeliving and reproductive active seabird’s populations. Four new herpesvirus were identified and called: Magellanic penguin herpesvirus 1 (MagHV -I), causing a mortality outbreak associated with necrotic-hemorrhagic tracheitis in Magellanic penguins in rehabilitation process; Magellanic penguin herpesvirus 2 (MagHV-2), identified in apparently healthy breeding Magellanic penguins at the Argentinean Patagonia’s colonies; Sulid herpesvirus 1 (SuHV-l), identified in boobies (Sula sp.) and tropicalseabirds (Phaeton sp.) breeding colonies at Abrolhos Archipelago, and Thalassarchid herpesvirus 1 (ThHV -1), identified in a yellow nose albatross (Thalassarche chlororhynchos) that appeared on the beaches of Rio Grande, RS, Brazil. Were. also identified: a new avipox named Brazilian penguinpox causing cutaneous, esophagus and respiratory lesions in rehabilitation penguins at Santa Catarina and the identification of two Santa Catarina and the identification of two Gammacoronavirus in three different asymptomatic seabirds species that were undergoing rehabilitation in Santa Catarina and Rio Grande do Sul. The data provi de a useful information basis for further studies related to pathology, virology, epidemiology and human impacts on southern hemispheres seabirds’ health.

Made available in DSpace on 2015-03-26T13:47:00Z (GMT). No. of bitstreams: 1 texto completo.pdf: 835531 bytes, checksum: 813caac126d354619ba3de602cddedc4 (MD5) Previous issue date: 2011-02-24 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / The Feline coronavirus (FCoV) is an enveloped virus RNA single-stranded, which belongs to the family Coronaviridae and the order Nidovirales. This virus is an important pathogen of wild and domestic cats and can cause a mild or inapparent enteric infection and also a rare and fatal disease called feline infectious peritonitis (FIP). The precise cause of FIP is still unknown but some hypotheses are suggested. The most accepted hypothesis is the theory of internal mutation that suggests a less virulent biotype of FCoV (FECV), would lead to other more pathogenic biotype (FIPV), capable of infecting monocytes and macrophages leading to FIP. However, despite being the most mentioned, there are still uncertainties in the relationship of the FCoV genome with the disease phenotype. This work presents a review from different FCoV studies attempt to elucidate existing theories on the pathogenesis of FCoV infection and tested through phylogenetic and phylogeographic approaches, the 7b gene of the first Brazilians FCoV sequences of asymptomatic and symptomatic cats in order to study the correlation between genetic diversity of this gene and differentiation of the two biotypes (FECV and FIPV). The 7b gene was shown to be highly conserved among the isolates and there was no differentiation between FIPV and FECV biotypes in phylogeographical and phylogenetic analysis, calling into question the theory of mutation. / O Feline coronavirus (FCoV) é um vírus envelopado de RNA fita simples, pertencente a família Coronaviridae e a ordem Nidovirales. Esse vírus é um importante patógeno de felinos domésticos e selvagens e pode causar uma inaparente ou leve infecção entérica e também causar uma doença imunomediada e fatal denominada peritonite infecciosa felina (PIF). A causa precisa da PIF ainda é desconhecida, mas algumas hipóteses são sugeridas. A hipótese mais aceita é a teoria da mutação interna que sugere que um biotipo menos virulento do FCoV (FECV), daria origem a outro biotipo mais patogênico (FIPV), capaz de infectar monócitos e macrófagos levando a PIF. Entretanto, apesar de ser a mais citada, ainda existem incertezas da relação do genoma do FCoV com o fenótipo da doença. Este trabalho, apresenta uma revisão com as diferentes pesquisas que tentam elucidar as teorias existentes sobre a patogênese da infecção pelo FCoV e testa, por meio de abordagens filogenética e filogeográfica, o gene 7b das primeiras sequências brasileiras de FCoV de gatos assintomáticos e sintomáticos, a fim de estudar, a correlação entre a diversidade genética desse gene e a diferenciação dos dois biotipos (FIPV e FECV). O gene 7b se mostrou altamente conservado entre os isolados virais e não houve diferenciação, na análise filogenética e filogeográfica, dos biotipos FIPV e FECV, pondo em questionamento a teoria da mutação.

Boletín que incluye información científica sobre el COVID-19, incluye artículos científicos y artículos preprint actualizados al 25 de Mayo de 2020.