Investigation of Novel Herpesvirus Felis catus Gammaherpesvirus 1: Salivary Shedding, Immune Evasion, and Manipulation of Cellular Gene Expression
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Notice bibliographique
Résumé
Herpesviruses are among the most ubiquitous vertebrate viruses and are defined both by their lifelong latent infections of the host cell, and their masterful manipulation of cellular processes including protein degradation, intracellular signalling, and gene expression. Herpesviruses have evolved alongside their hosts and control host cell functions through a varied array of mechanisms, often through protein-protein interactions. Herpesviruses are transmitted predominantly through infected bodily fluids including saliva and typically exist asymptomatically within the host. However, lytic replication triggered by chemical or physiological factors may result in a diverse set of pathologies. The lymphotropic herpesvirus sub-family, gammaherpesviruses (GHV), also contribute to a range of pathologies in humans and animals including fatal cancers. To improve our understanding of both the prevalence of GHVs and their manipulation of host cellular processes, we investigated the epidemiological characteristics of a novel feline GHV, called Felis catus gammaherpesvirus 1 (FcaGHV1), as well as the function and mechanism of two novel FcaGHV1 proteins through a range of molecular biology methods. We found that FcaGHV1 glycoprotein B (gB) DNA was shed in domestic feline saliva from cats in southwest Ontario with a frequency similar to published literature. We also confirmed conservation of FcaGHV1 gB in southwest Ontario to other FcaGHV1 isolates worldwide, and attempted isolation of FcaGHV1 in cell culture. Furthermore, we elucidated the function and mechanism of the viral E3 ligase F10, which downregulates host surface MHC-I to aid viral survival by immune evasion through an endoplasmic reticulum-associated degradation-dependent and proteasome-dependent mechanism. Finally, we characterized the putative mechanism of F20, a novel FcaGHV1 ORF categorized as an “ORFan” due to its lack of homology to any published genes or protein. F20 triggers widespread host gene downregulation, potentially through manipulation of host p38 and JNK MAPK signalling via virus-host protein interactions. Our results warrant further investigation of FcaGHV1 epidemiology and the mechanisms of its repertoire of novel ORFs and proteins. Our work contributes to the growing knowledge pool of GHV prevalence and shedding, as well as the mechanisms by which GHVs manipulate host cell processes to aid viral survival and replication.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle