Investigation of Novel Herpesvirus Felis catus Gammaherpesvirus 1: Salivary Shedding, Immune Evasion, and Manipulation of Cellular Gene Expression
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".