Cell-Dependent Mechanisms Restrict the HIV Type 1 Coreceptor Activity of US28, a Chemokine Receptor Homolog Encoded by Human Cytomegalovirus
Bibliographic record
Abstract
Several members of the chemokine receptor family are used together with CD4 for HIV-1 entry into target cells. The human cytomegalovirus US28 gene encodes a chemokine receptor homolog that has been reported to function as an HIV-1 coreceptor. However, studies of US28 have given conflicting results regarding its ability to mediate HIV-1 entry. We examined the ability of US28 to function as an HIV-1 coreceptor in various cell lines and found that its coreceptor activity is highly cell dependent. US28 could function as a coreceptor for HIV-1 entry in HeLa and U87 cells but not in COS-1 and Cf2Th cells. In COS-1 cells, US28 was expressed on the cell surface and could mediate cell-cell fusion with HIV-1 Env-expressing cells, suggesting that the block to infection may result from a defect in virus internalization or postentry steps. In Cf2Th cells, US28 was expressed at high levels intracellularly but was not transported to the cell surface. The block in US28 coreceptor function in COS-1 and Cf2Th cells was coreceptor dependent, since CCR5, CXCR4, and other coreceptors can mediate HIV-1 entry in these cell lines. HIV-1 viruses pseudotyped with the MuLV or VSV Env entered and replicated at similar efficiency in COS-1 and U87 cells in single-cycle infections, suggesting that postentry and other early events in the HIV-1 life cycle are not intrinsically inefficient in COS-1 cells. These results identify two distinct mechanisms that can restrict the HIV-1 coreceptor activity of US28 in a cell- and coreceptor-dependent manner, and help to explain the existing controversy regarding the ability of US28 to mediate HIV-1 entry.
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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".