Details

Autor(en) / Beteiligte

• Lanteri, Marion
• Vahidnia, Farnaz
• Tan, Sylvia
• Stapleton, Jack
• Norris, Philip J.
• Heitman, John W.
• Deng, Xutao
• Keating, Sheila
• Brambilla, Donald
• Busch, Michael
• Custer, Brian

Titel

Downregulation of Cytokines and Chemokines By GB Virus C after Transfusion-Transmission in HIV+ Blood Recipients

Ist Teil von

• Blood, 2014-12, Vol.124 (21), p.4122-4122

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• ▪ Background: An association between GBV-C and improved HIV-infection outcome has been reported in HIV+ individuals with active GBV-C co-infection. The host immunological response underlying GBV-C and HIV co-infection that results in better HIV survival is not well characterized. This longitudinal study provides insight into the immune mechanisms underlying the potential protective role of GBV-C in HIV infected patients. Methods: Concentrations of 64 cytokines and chemokines were measured in plasma samples from the Viral Activation Transfusion Study (VATS) cohort before and longitudinally after GBV-C acquisition in 30 HIV+/GBV-C+ cases and 30 HIV+/GBV-C- controls up to 15 months following first transfusion. Adjusted mixed modeling was used to analyze the impact of GBV-C infection on cytokine/chemokine concentrations over time, adjusting for time elapsed, HAART treatment status, HIV VL, and subject. Pathway Analysis (PA; Qiagen Ingenuity Pathway Analysis) was performed to help predict what effect the observed cytokine changes might have on the host immune system. Results: A significant decrease in HIV VL was observed in HIV+/GBV-C+ cases from a mean log10(HIV VL) = 4.33 at baseline down to 3.24 at 100 days post-GBV-C detection (p<0.01) and maintained at 3.39 at 300 days post-GBV-C detection (p=0.02). GBV-C+/HIV+ cases had higher CD4 T cell counts than controls after acquisition of GBV-C infection. At baseline, there was no significant difference between HIV+/GBV-C+ cases and HIV+/GBV-C- controls in cytokine/chemokine levels. Most of the modulated cytokines and chemokines were reduced post-GBV-C detection, including many pro-inflammatory cytokines, suggesting an overall anti-inflammatory effect of GBV-C after co-infection in HIV+ subjects (Figure 1). After adjustment for HIV VL and HAART status, GBV-C infection significantly associated with decreases in the levels of nine cytokines (p<0.05 and FDR≤0.2): one anti-inflammatory cytokines IL-10 , two pro-inflammatory cytokines IL-6 and IL-7, four chemo-attractants MIP-1α, 6Ckine, I-TAC and GCP-2, and the growth factor SCF (Figure 2). Pathway Analysis showed HIV+/GBV-C+ cases had an enrichment in genes associated with cell death and apoptosis pathways of various cells (phagocytes, leukocytes including T cells, myeloid cells, dendritic cells, granulocytes, APC, neutrophils, neuroglia) and in the development of phagocytes and function of APCs and a decrease in binding, migration, and movement of cells within 3 months post-GBV-C detection. Similarly, 300 days post-GBV-C detection, there was a further decrease in cellular activation (PBMCs, myeloid cells) and cellular trafficking with an increase in the proliferation of myeloid progenitor cells and leukocyte infection. Conclusion: GBV-C has a protective effect in part through a competition mechanism leading to decreased inflammation and improved HIV disease outcome in GBV-C+/HIV+ individuals. Further studies are necessary to establish whether this purportedly non-pathogenic virus causing immune down-regulation could have deleterious effects on the host at the cellular level, including depleting the cells which are HIV targets. [Display omitted] [Display omitted] No relevant conflicts of interest to declare.