Frequency and significance of HIV-1 infection of CD8+ T-cells: Implications for viral pathogenesis
Bibliographic record
Abstract
To date, the effect of HIV-1 infection on CD8+ T-cells remains poorly studied. Previous studies have shown that the effector functions of CD8+ T-cells diminish during AIDS. We postulated that CD8+ T-cell functions decrease due to the tropism of HIV-1 for CD8+ T-cells. Therefore we examined whether CD8+ T-cells provide suitable targets for HIV-1 infection and the mechanism(s) by which the virus enters the cells. We hypothesized that HIV-1 entry into these cells may be facilitated through access to extracellular receptors. Ex vivo experiments were performed using blood samples from a cohort of HIV-1 infected patients attending the Ottawa Hospital Immunodeficiency Clinic. Frequency of HIV-1 infection was monitored by flow cytometric detection of HIV-1 p24 antigen and viral production from separated CD8+ and CD4+ T-cell lineages was assayed by the quantitation of viral RNA transcripts. Primary CD8+ T-cells and CD8+ T-cell clones used in the in vitro studies were isolated from the peripheral blood of healthy volunteers. HIV-1 infection was monitored by both ELISA and flow cytometric analyses. Similarly, receptor analysis was performed by flow cytometry and confirmed by RT-PCR analysis. There was a significantly higher frequency of CD8+HIV+ cells than CD4+HIV+ cells found in the ex vivo studies of patient samples, however, viral production from the CD8+HIV+ subset was 2-3 logs lower than that found in CD4+HIV+ T-cells. In addition, CD8+ T-cells served as suitable targets for productive HIV-1 infection in vitro and preferential HIV-1 replication occurred in the memory T-cell subset. Interestingly, the HTLV-I transformed CD8+ T-cell clones exhibited HIV-1 production 20-fold greater than CD4+ T-cells. Our research also demonstrated that during the course of infection, there was a decrease in mean expression of the CD8 and CXCR4 cell-surface molecules in the HIV-1 infected CD8+ T-cell clones. Accordingly, the use of antibodies to the CD8 or CXCR4 molecules eradicated viral adsorption and replication in the CD8+ T-cell clones. Our research was the first to demonstrate the significance and susceptibility of CD8+ T-cells to HIV-1 infection through both ex vivo and in vitro analyses. We conclude, with multiple lines of evidence detecting and measuring HIV-1 infection of CD8+ T-lymphocytes, that this cellular target and reservoir may be central to HIV-1 pathogenesis. By identifying a novel target of HIV-1 and potential cellular receptors used by the virus, future therapeutic strategies may be designed to help prevent and treat HIV-1 infection.
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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 | 0.001 |
| 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 | 0.001 | 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".