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Supplemental Digital Content is Available in the Text. Background: HIV type 1 ((human immunodeficiency virus) HIV-1) elite controllers (ECs) are a rare subset of people living with HIV-1 (PLWH) who control viral replication in the absence of antiretroviral treatment (ART) and may provide a model for a functional cure. We investigated the role of natural killer (NK) cells in HIV-1 ECs from South Africa. Methods: Phenotypic (CD69, CD38, CD57, PD-1), functional (CD107a, IFN-γ (inferferon gamma)), and nutrient transporter profiles (glucose transporter 1, CD98) of NK cells from ECs (n = 20), viremic progressors (VPs; n = 19), PLWH on ART (n = 20), and people without HIV-1 (PWOH; n = 21) were analyzed using flow cytometry. The Kruskal–Wallis test and followed by the Mann–Whitney U test were used to determine differences among the study groups. The Spearman rank correlation coefficient was used to determine significant associations. Results: Compared with the other study groups, the percentage of CD69-expressing NK cells was higher in ECs, whereas the percentage of CD38-expressing NK cells was higher in VPs. Percentages of CD69+CD38− NK cells were elevated in ECs compared with VPs (P = 0.003), but were not different to PLWH on ART and PWOH. Differentiation, exhaustion, and metabolic profiles were not different in ECs compared with PLWH on ART and PWOH; however, NK cell function was lower than in PWOH. Conclusions: These findings demonstrate that NK cells from ECs have an activated, mature profile with low levels of immune exhaustion and a reduced metabolic phenotype suggesting functional competence. This insight could inform the development of novel immunotherapeutic strategies for treating HIV-1. [ABSTRACT FROM AUTHOR]

Background: Rift Valley fever (RVF) is a mosquito-borne viral zoonosis affecting domestic and wild ruminants, camels and humans. Outbreaks of RVF are characterized by a sudden onset of abortions and high mortality amongst domestic ruminants. Humans develop disease ranging from a mild flu-like illness to more severe complications including hemorrhagic syndrome, ocular and neurological lesions and death. During the RVF outbreak in South Africa in 2010/11, a total of 278 human cases were laboratory confirmed, including 25 deaths. The role of the host inflammatory response to RVF pathogenesis is not completely understood. Methods: Virus load in serum from human fatal and non-fatal cases was determined by standard tissue culture infective dose 50 (TCID50) titration on Vero cells. Patient serum concentration of chemokines and cytokines involved in inflammatory responses (IL-8, RANTES, CXCL9, MCP-1, IP-10, IL-1β, IL-6, IL-10, TNF and IL-12p70) was determined using cytometric bead assays and flow cytometry. Results: Fatal cases had a 1-log10 higher TCID50/ml serum concentration of RVF virus (RVFV) than survivors (p < 0.05). There were no significant sequence differences between isolates recovered from fatal and non-fatal cases. Chemokines and pro- and anti-inflammatory cytokines were detected at significantly increased (IL-8, CXCL9, MCP-1, IP-10, IL-10) or decreased (RANTES) levels when comparing fatal cases to infected survivors and uninfected controls, or when comparing combined infected patients to uninfected controls. Conclusions: The results suggest that regulation of the host inflammatory responses plays an important role in the outcome of RVFV infection in humans. Dysregulation of the inflammatory response contributes to a fatal outcome. The cytokines and chemokines identified in this study that correlate with fatal outcomes warrant further investigation as markers for disease severity. [ABSTRACT FROM AUTHOR]

Background: Understanding the role of different classes of T cells during HIV infection is critical to determining which responses correlate with protective immunity. To date, it is unclear whether alterations in regulatory T cell (Treg) function are contributory to progression of HIV infection. Methodology: FOXP3 expression was measured by both qRT-PCR and by flow cytometry in HIV-infected individuals and uninfected controls together with expression of CD25, GITR and CTLA-4. Cultured peripheral blood mononuclear cells were stimulated with anti-CD3 and cell proliferation was assessed by CFSE dilution. Principal Findings: HIV infected individuals had significantly higher frequencies of CD4+FOXP3+ T cells (median of 8.11%; range 1.33%-26.27%) than healthy controls (median 3.72%; range 1.3-7.5%; P = 0.002), despite having lower absolute counts of CD4+FOXP3+ T cells. There was a significant positive correlation between the frequency of CD4+FOXP3+ T cells and viral load (rho = 0.593 P = 0.003) and a significant negative correlation with CD4 count (rho =20.423 P = 0.044). 48% of our patients had CD4 counts below 200 cells/ml and these patients showed a marked elevation of FOXP3 percentage (median 10% range 4.07%-26.27%). Assessing the mechanism of increased FOXP3 frequency, we found that the high FOXP3 levels noted in HIV infected individuals dropped rapidly in unstimulated culture conditions but could be restimulated by T cell receptor stimulation. This suggests that the high FOXP3 expression in HIV infected patients is likely due to FOXP3 upregulation by individual CD4+ T cells following antigenic or other stimulation. Conclusions/Significance: FOXP3 expression in the CD4+ T cell population is a marker of severity of HIV infection and a potential prognostic marker of disease progression. [ABSTRACT FROM AUTHOR]

The article studies CC chemokines in the context of their ability to influence or instruct adaptive anti-HIV T-cell immune responses in HIV-1-infected individuals. It attempts to determine whether gene duplications of CCL3L1, selected as a measure of host CCL3 chemokine production capacity, influenced the integrity of HIV-1-specific CD4 and CD8 T-cell responses and viral load in HIV-1-infected women.

Objective: CCR5-tropic viruses are preferentially transmitted during perinatal HIV-1 infection. CCR5 density on CD4 + T-cells likely impacts susceptibility to HIV-1 infection., Design: Fifty-two mother-infant dyads were enrolled. All mothers were living with HIV-1, 27 of the infants acquired HIV-1 in utero and 25 infants remained uninfected., Methods: CCR5 density, together with frequencies of CD4 + and CD8 + T-cells expressing immune activation (CCR5, ICOS and HLA-DR) and immune checkpoint (TIGIT and PD-1) markers, were measured in whole blood from the dyads close to delivery., Results: Compared with mothers who did not transmit, mothers who transmitted HIV-1 had less exposure to ART during pregnancy ( P = 0.015) and higher plasma viral load close to delivery ( P = 0.0005). These mothers, additionally, had higher CCR5 density on CD4 + and CD8 + T-cells and higher frequencies of CCR5, ICOS and TIGIT-expressing CD8 + T-cells. Similarly, compared with infants without HIV-1, infants with HIV-1 had higher CCR5 density on CD4 + and CD8 + T-cells and higher frequencies of CCR5, TIGIT, and PD-1-expressing CD4 + and CD8 + T-cells as well as higher frequencies of HLA-DR-expressing CD8 + T-cells. CCR5 density on maternal CD4 + T-cells remained significantly associated with transmission after adjusting for maternal viral load and CD4 + T cell counts. Mother-infant dyads with shared high CCR5 density phenotypes had the highest risk of transmission/acquisition of infection compared with dyads with shared low-CCR5 density phenotypes., Conclusion: This study provides strong evidence of a protective role for a combined mother-infant low CD4 + T-cell CCR5 density phenotype in in-utero transmission/acquisition of HIV-1., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Cross-sectional analysis of human immunodeficiency virus-exposed, uninfected infants revealed high proportions of CXCR4-expressing cells in their cord blood, which declined at 4.5 months and increased between 9 and 15 months to levels approaching those of uninfected adults. Proportions of CCR5-expressing cells, however, were very low in cord blood and subsequently increased with age.