Divergent susceptibilities of human herpesvirus 6 variants to type I interferons
Bibliographic record
Abstract
Two distinct human herpesvirus 6 (HHV-6) variants infect humans. HHV-6B is the etiologic agent of roseola and is associated with life-threatening neurological diseases, such as encephalitis, as well as organ transplant failure. The epidemiology and disease association for HHV-6A remain ill-defined. Specific anti-HHV-6 drugs do not exist and classic antiherpes drugs have secondary effects that are often problematic for transplant patients. Clinical trials using IFN were also performed with inconclusive results. We investigated the efficacy of type I IFN (alpha/beta) in controlling HHV-6 infection. We report that cells infected with laboratory strains and primary isolates of HHV-6B are resistant to IFN-alpha/beta antiviral actions as a result of improper IFN-stimulated gene (ISGs) expression. In contrast, HHV-6A-infected cells were responsive to IFN-alpha/beta with pronounced antiviral effects observed. Type II IFN (gamma)-signaling was unaltered in cells infected by either variant. The HHV-6B immediate-early 1 (IE1) physically interacts with STAT2 and sequestrates it to the nucleus. As a consequence, IE1B prevents the binding of ISGF3 to IFN-responsive gene promoters, resulting in ISG silencing. In comparison, HHV-6A and its associated IE1 protein displayed marginal ISG inhibitory activity relative to HHV-6B. The ISG inhibitory domain of IE1B mapped to a 41 amino acid region absent from IE1A. Transfer of this IE1B region resulted in a gain of function that conferred ISG inhibitory activity to IE1A. Our work is unique in demonstrating type I IFN signaling defects in HHV-6B-infected cells and highlights a major biological difference between HHV-6 variants.
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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) | 0.001 | 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".