Rapid Progressing Allele HLA-B35 Px Restricted Anti-HIV-1 CD8+ T Cells Recognize Vestigial CTL Epitopes

BACKGROUND: The HLA-B*35-Px allele has been associated with rapid disease progression in HIV-1 infection, in contrast to the HLA-B*35-Py allele. METHODOLOGY/PRINCIPAL FINDINGS: Immune responses to two HLA-B*35 restricted HIV-1 specific CTL epitopes and their variants were followed longitudinally during early HIV-1 infection in 16 HLA-B*35+ individuals. Subjects expressing HLA-B*35-Px alleles showed no difference in response to the consensus epitopes compared to individuals with HLA-B*35-Py alleles. Surprisingly, all the HLA-B*35-Px+ individuals responded to epitope-variants even in the absence of a consensus response. Sequencing of the viral population revealed no evidence of variant virus in any of the individuals. CONCLUSIONS/SIGNIFICANCE: This demonstrates a novel phenomenon that distinguishes individuals with the HLA-B*35-Px rapid progressing allele and those with the HLA-B*35-Py slower progressing allele

R5 Human Immunodeficiency Virus Type 1 (HIV-1) Replicates More Efficiently in Primary CD4(+) T-Cell Cultures Than X4 HIV-1

In this report, we present evidence that R5 human immunodeficiency virus type 1 (HIV-1) replicates more efficiently in primary CD4(+) T cells than X4 HIV-1. By comparing CD3/CD28-costimulated CD4(+) T-cell cultures infected by several X4 and R5 HIV-1 strains, we determined that R5-infected CD4(+) T cells produce more virus over time than X4-infected CD4(+) T cells. In the first comparison, we found that more cells were infected by the X4-tropic strain LAI than by the R5-tropic strain JR-CSF and yet that higher levels of viral production were detected in the R5-infected cultures. The differential viral production was partially due to the severe cytopathic effects of the X4 virus. We also compared cultures infected with the isogenic HIV-1 strains NL4-3 (X4) and 49.5 (R5). We found that fewer cells were infected by the R5 strain, and yet similar levels of viral production were detected in both infected cultures. Cell death played less of a role in the differential viral production of these strains, as the cell viability remained comparable in both X4- and R5-infected cultures over time. The final comparison involved the primary R5-tropic isolate KP1 and the primary dual-tropic isolate KP2. Although both strains infected similar numbers of cells and induced comparable levels of cytopathicity, viral production was considerably higher in the R5-infected culture. In summary, these data demonstrate that R5 HIV-1 has an increased capacity to replicate in costimulated CD4(+) T cells compared to X4 HIV-1

Correction: Rapid Progressing Allele HLA-B35 Px Restricted Anti-HIV-1 CD8+ T Cells Recognize Vestigial CTL Epitopes

[This corrects the article DOI: 10.1371/journal.pone.0010249.]

Correction: Rapid Progressing Allele HLA-B35 Px Restricted Anti-HIV-1 CD8+ T Cells Recognize Vestigial CTL Epitopes.

[This corrects the article DOI: 10.1371/journal.pone.0010249.]

CD8+ T cell IFN-γ responses to both consensus epitopes (solid bars, TY9 green and VY10 orange), and variant epitopes (TY9 variants green, checkered or stripped bars, and VY10 variant orange checkered bars).

<p>Representative examples of longitudinal responses are shown for HLA-B*35 -Px+ Subjects 1 (A) and 2 (B), and HLA-B*35 -Py+ Subject 8 (C). CD8+ T cell IFN-γ responses from Subject 6, who expressed both HLA-B*35 -Px and -Py alleles (D). HLA-B*35 -Px+ individuals did not display unusual CD4 counts or viral loads, a representative example shown from Subject 1 (E).</p

HIV-1 Pol Sequencing of HLA-B*35 -Px allele expressing individuals.

<p>HIV-1 Pol Sequencing of HLA-B*35 -Px allele expressing individuals.</p

Clinical parameters, average CD4 and viral load (VL) were generated from across the entire study window.

<p>Clinical parameters, average CD4 and viral load (VL) were generated from across the entire study window.</p