Author response: Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation
Bibliographic record
Abstract
Cytomegalovirus (CMV) is one of eight herpesviruses that can infect humans. Most people will at some point become infected with CMV, yet the virus tends only to cause serious disease in people whose immune system is not working properly. Individuals living with HIV/AIDS and organ transplant recipients (who have to take drugs that suppress their immune system to prevent the organ being rejected) are particularly vulnerable to CMV infections. Critically, the virus can cross the placenta to infect of the foetus. CMV infection in the womb can cause miscarriage, lead to severe developmental problems in babies and is a major cause of deafness. Herpesvirus infections are for life. While the immune system cannot eliminate CMV, it does have many systems that combine to sense and control infections. Natural killer cells are known to play a critical role in detecting and destroying cells infected with CMV. The virus, in turn, has nine genes that help to protect it against natural killer cells. This includes two genes that belong to a group of similar genes called the US12 family, but it is not clear whether other members of this gene family also provide protection against natural killer cells. Fielding et al. now show that at least four members of the US12 gene family help CMV to evade natural killer cells. For example, two members work together to target a human protein called B7-H6 that acts a sensor to alert natural killer cells if a particular cell is infected. However, the impact of the US12 family goes even wider. The whole family works together to control proteins that are found on the surface of human cells, and many of these proteins appear to be involved in regulating the immune response. The findings of Fielding et al. provide an insight into how the US12 gene family works, and how CMV has evolved to escape the human immune system. New therapies to control CMV infections are urgently needed so the next challenge is to design new antiviral agents that will target CMV’s defence systems.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.292 | 0.132 |
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".