CD71 <sup>+</sup> erythroid cells exacerbate HIV-1 infection by reactive oxygen species and trans-infect HIV to CD4 <sup>+</sup> T cells
Bibliographic record
Abstract
Abstract CD71 + erythroid cells (CECs) have a wide range of immunomodulatory properties but their potential role in HIV has never been investigated before. Here, we demonstrate that CECs are abundant in the human cord blood, placental tissue and peripheral blood of pregnant mothers. We found that CECs exacerbate HIV-1 infection/replication when co-cultured with CD4 + T cells; and that pre-exposure of CD4 + T cells to CECs make them more permissible to HIV-infection. Our observations indicate how interactions of CECs with CD4 + T cells via reactive oxygen species (ROS)-dependent mechanism results in the upregulation of NF-kB, which affects the cell cycle machinery to facilitate HIV-1 replication. We found the complement receptor-1 (CD35) and the Duffy antigen receptor for chemokines (DARC) as potential HIV-target molecules are expressed significantly higher on CECs compared to mature red blood cells. However, blocking CD35 or DARC did not inhibit HIV-1 trans-infection to uninfected CD4 + T cells. We demonstrate that CECs bind to HIV-1 via CD235a and subsequently trans-infect the virus to uninfected CD4 + T cells. In addition, we found significant abundance of CECs in the blood of HIV-1 infected and anemic subjects, which enhanced HIV infection/replication in autologous CD4 + T cells similar to what we observed for the cord blood and placenta-derived CECs. In agreement, a positive correlation between the frequency of CECs with the plasma viral load in HIV-1 infected antiretroviral therapy naïve individuals was observed. In addition, we found that CECs even in the presence of Tenofovir, can trans-infect HIV-1 to CD4 + T cells. Our studies provide a novel insight into the role of CECs in HIV pathogenesis as potential contributing cells for viral persistence in the presence of antiretroviral therapy. Author summary Despite current antiretroviral therapy, HIV-1 persists in a small pool of infected cells. A better understanding of HIV-reservoirs and influence of other non-immune cells on HIV-1 replication and transmission is a pre-requisite to the development of HIV-eradication strategies. Immature red blood cells (CD71 + erythroid cells) are physiologically abundant in newborns, cord blood, placenta and blood of pregnant women, with a wide range of immunological properties. This study demonstrates that these cells not only enhance HIV-1 infection/replication by reactive oxygen species in HIV-target cells (CD4 + T cells) but also bind to HIV and trans-infect the virus to the target cells in the presence of Tenofovir, an HIV drug. We found that these immature red blood cells are abundant in the blood of HIV-patients and anemic individuals. In addition, we observed a positive correlation between the levels of plasma viral load with the frequency of immature red blood cells in HIV-infected individuals. Therefore, our studies discover a novel role for these immature red blood in HIV pathogenesis, which encourages efforts to target these cells as adjuncts of current treatment strategies.
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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) | 0.002 | 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".