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Plasmodium infection reduces the volume of the viral reservoir in SIV-infected rhesus macaques receiving antiretroviral therapy.

Zhan XY, Wang N, Liu G, Qin L, Xu W, Zhao S, Qin L, Chen X - Retrovirology (2014)

Bottom Line: This reduction might be attributable to malaria-mediated activation and apoptotic induction of memory CD4+ T cells.Further studies indicated that histone acetylation and NF-kappaB (NF-κB) activation in resting CD4+ T cells may also play an important role in this reduction.As more HIV-1-infected individuals in malaria-endemic areas receive ART, we should explore whether any of the patients co-infected with Plasmodium experience virologic benefits.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Luogang District, Guangzhou Science Park, Guangzhou, 510530, Guangdong Province, China. zhan_xiaoyong@gibh.ac.cn.

ABSTRACT

Background: Previous studies indicated that Plasmodium infection activates the immune system, including memory CD4+ T cells, which constitute the reservoir of human immunodeficiency virus type-1 (HIV-1). Therefore, we postulated that co-infection with malaria might activate the reservoir of HIV-1. To test this hypothesis, we used a rhesus macaque model of co-infection with malaria and simian immunodeficiency virus (SIV), along with antiretroviral therapy (ART).

Results: Our results showed that Plasmodium infection reduced both the replication-competent virus pool in resting CD4+ T cells and the integrated virus DNA (iDNA) load in peripheral blood mononuclear cells in the monkeys. This reduction might be attributable to malaria-mediated activation and apoptotic induction of memory CD4+ T cells. Further studies indicated that histone acetylation and NF-kappaB (NF-κB) activation in resting CD4+ T cells may also play an important role in this reduction.

Conclusions: The findings of this work expand our knowledge of the interaction between these two diseases. As more HIV-1-infected individuals in malaria-endemic areas receive ART, we should explore whether any of the patients co-infected with Plasmodium experience virologic benefits.

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Related in: MedlinePlus

In vitroassays measuring the apoptosis and activation of monkey memory CD4+ T cells by Pf extract. PBMCs from a monkey with chronic SIV infection were isolated and cocultured with Pf extract. After coculture for 24 or 48 hours, the cells were stained with anti-CD4 PE-Cy7, anti-CD95-APC, and annexin V PE or with anti-CD4 PE-Cy7, anti-CD95 APC, anti-CD38 FITC and anti-HLA-DR PE. Memory CD4+ T cells were gated (CD95 + CD4+ T lymphocytes) and examined for the percentages of cells that stained with annexin V. Alternatively, the MFI of CD38 and HLA-DR was measured. (A) Both 10 μg/ml and 50 μg/ml Pf extract could dramatically induce the apoptosis of memory CD4+ T cells after 48 hours of coculture (3.30 ± 0.20% vs. 1.23 ± 0.07% and 4.36 ± 1.10% vs. 1.23 ± 0.07%, respectively, P < 0.001). (B) In this study, 50 μg/ml Pf extract could induce the activation of memory CD4+ T cells, leading to more CD38 (MFI of 100.50 ± 4.50 vs. 75.27 ± 1.25) and HLA-DR (MFI of 226.00 ± 7.00 vs. 146.00 ± 2.000) expression on these cells after 48 hours of coculture. (C) A positive correlation was found between the memory CD4+ T cells’ activation level and apoptosis level. (D) In this study, 50 μg/ml Pf extract could induce more SIV p27 antigen expression after 8 days of coculture (181.70 ± 57.08 vs. 47.11 ± 12.75 pg/ml). The data in this figure are presented as the means with SD. One-way ANOVA was used to compare the variables in A, B and D. Spearman’s correlation analysis was used to analyze the relationship between the parameters in C.
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Fig8: In vitroassays measuring the apoptosis and activation of monkey memory CD4+ T cells by Pf extract. PBMCs from a monkey with chronic SIV infection were isolated and cocultured with Pf extract. After coculture for 24 or 48 hours, the cells were stained with anti-CD4 PE-Cy7, anti-CD95-APC, and annexin V PE or with anti-CD4 PE-Cy7, anti-CD95 APC, anti-CD38 FITC and anti-HLA-DR PE. Memory CD4+ T cells were gated (CD95 + CD4+ T lymphocytes) and examined for the percentages of cells that stained with annexin V. Alternatively, the MFI of CD38 and HLA-DR was measured. (A) Both 10 μg/ml and 50 μg/ml Pf extract could dramatically induce the apoptosis of memory CD4+ T cells after 48 hours of coculture (3.30 ± 0.20% vs. 1.23 ± 0.07% and 4.36 ± 1.10% vs. 1.23 ± 0.07%, respectively, P < 0.001). (B) In this study, 50 μg/ml Pf extract could induce the activation of memory CD4+ T cells, leading to more CD38 (MFI of 100.50 ± 4.50 vs. 75.27 ± 1.25) and HLA-DR (MFI of 226.00 ± 7.00 vs. 146.00 ± 2.000) expression on these cells after 48 hours of coculture. (C) A positive correlation was found between the memory CD4+ T cells’ activation level and apoptosis level. (D) In this study, 50 μg/ml Pf extract could induce more SIV p27 antigen expression after 8 days of coculture (181.70 ± 57.08 vs. 47.11 ± 12.75 pg/ml). The data in this figure are presented as the means with SD. One-way ANOVA was used to compare the variables in A, B and D. Spearman’s correlation analysis was used to analyze the relationship between the parameters in C.

Mentions: Figure 8A and B show the potency of Pf 3d7 extract in inducing the activation and apoptosis of monkey memory CD4+ T cells. The results showed that Pf extract could induce the apoptosis of memory CD4+ T cells and the activation of these cells. Specifically, more expression of the activation marker CD38 and HLA-DR was found after co-incubation with Pf extract (Figure 8A and B). Correlation analysis showed that the apoptosis of memory CD4+ T cells positively correlated with the activation level of these cells (Figure 8C). Pf dd2 extract had similar potency in inducing the activation and apoptosis of monkey memory CD4+ T cells (data not shown). In addition, more expression of the SIV antigen p27 protein was induced after 8 days of culture with Pf extract (Figure 8D).Figure 8


Plasmodium infection reduces the volume of the viral reservoir in SIV-infected rhesus macaques receiving antiretroviral therapy.

Zhan XY, Wang N, Liu G, Qin L, Xu W, Zhao S, Qin L, Chen X - Retrovirology (2014)

In vitroassays measuring the apoptosis and activation of monkey memory CD4+ T cells by Pf extract. PBMCs from a monkey with chronic SIV infection were isolated and cocultured with Pf extract. After coculture for 24 or 48 hours, the cells were stained with anti-CD4 PE-Cy7, anti-CD95-APC, and annexin V PE or with anti-CD4 PE-Cy7, anti-CD95 APC, anti-CD38 FITC and anti-HLA-DR PE. Memory CD4+ T cells were gated (CD95 + CD4+ T lymphocytes) and examined for the percentages of cells that stained with annexin V. Alternatively, the MFI of CD38 and HLA-DR was measured. (A) Both 10 μg/ml and 50 μg/ml Pf extract could dramatically induce the apoptosis of memory CD4+ T cells after 48 hours of coculture (3.30 ± 0.20% vs. 1.23 ± 0.07% and 4.36 ± 1.10% vs. 1.23 ± 0.07%, respectively, P < 0.001). (B) In this study, 50 μg/ml Pf extract could induce the activation of memory CD4+ T cells, leading to more CD38 (MFI of 100.50 ± 4.50 vs. 75.27 ± 1.25) and HLA-DR (MFI of 226.00 ± 7.00 vs. 146.00 ± 2.000) expression on these cells after 48 hours of coculture. (C) A positive correlation was found between the memory CD4+ T cells’ activation level and apoptosis level. (D) In this study, 50 μg/ml Pf extract could induce more SIV p27 antigen expression after 8 days of coculture (181.70 ± 57.08 vs. 47.11 ± 12.75 pg/ml). The data in this figure are presented as the means with SD. One-way ANOVA was used to compare the variables in A, B and D. Spearman’s correlation analysis was used to analyze the relationship between the parameters in C.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Fig8: In vitroassays measuring the apoptosis and activation of monkey memory CD4+ T cells by Pf extract. PBMCs from a monkey with chronic SIV infection were isolated and cocultured with Pf extract. After coculture for 24 or 48 hours, the cells were stained with anti-CD4 PE-Cy7, anti-CD95-APC, and annexin V PE or with anti-CD4 PE-Cy7, anti-CD95 APC, anti-CD38 FITC and anti-HLA-DR PE. Memory CD4+ T cells were gated (CD95 + CD4+ T lymphocytes) and examined for the percentages of cells that stained with annexin V. Alternatively, the MFI of CD38 and HLA-DR was measured. (A) Both 10 μg/ml and 50 μg/ml Pf extract could dramatically induce the apoptosis of memory CD4+ T cells after 48 hours of coculture (3.30 ± 0.20% vs. 1.23 ± 0.07% and 4.36 ± 1.10% vs. 1.23 ± 0.07%, respectively, P < 0.001). (B) In this study, 50 μg/ml Pf extract could induce the activation of memory CD4+ T cells, leading to more CD38 (MFI of 100.50 ± 4.50 vs. 75.27 ± 1.25) and HLA-DR (MFI of 226.00 ± 7.00 vs. 146.00 ± 2.000) expression on these cells after 48 hours of coculture. (C) A positive correlation was found between the memory CD4+ T cells’ activation level and apoptosis level. (D) In this study, 50 μg/ml Pf extract could induce more SIV p27 antigen expression after 8 days of coculture (181.70 ± 57.08 vs. 47.11 ± 12.75 pg/ml). The data in this figure are presented as the means with SD. One-way ANOVA was used to compare the variables in A, B and D. Spearman’s correlation analysis was used to analyze the relationship between the parameters in C.
Mentions: Figure 8A and B show the potency of Pf 3d7 extract in inducing the activation and apoptosis of monkey memory CD4+ T cells. The results showed that Pf extract could induce the apoptosis of memory CD4+ T cells and the activation of these cells. Specifically, more expression of the activation marker CD38 and HLA-DR was found after co-incubation with Pf extract (Figure 8A and B). Correlation analysis showed that the apoptosis of memory CD4+ T cells positively correlated with the activation level of these cells (Figure 8C). Pf dd2 extract had similar potency in inducing the activation and apoptosis of monkey memory CD4+ T cells (data not shown). In addition, more expression of the SIV antigen p27 protein was induced after 8 days of culture with Pf extract (Figure 8D).Figure 8

Bottom Line: This reduction might be attributable to malaria-mediated activation and apoptotic induction of memory CD4+ T cells.Further studies indicated that histone acetylation and NF-kappaB (NF-κB) activation in resting CD4+ T cells may also play an important role in this reduction.As more HIV-1-infected individuals in malaria-endemic areas receive ART, we should explore whether any of the patients co-infected with Plasmodium experience virologic benefits.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Luogang District, Guangzhou Science Park, Guangzhou, 510530, Guangdong Province, China. zhan_xiaoyong@gibh.ac.cn.

ABSTRACT

Background: Previous studies indicated that Plasmodium infection activates the immune system, including memory CD4+ T cells, which constitute the reservoir of human immunodeficiency virus type-1 (HIV-1). Therefore, we postulated that co-infection with malaria might activate the reservoir of HIV-1. To test this hypothesis, we used a rhesus macaque model of co-infection with malaria and simian immunodeficiency virus (SIV), along with antiretroviral therapy (ART).

Results: Our results showed that Plasmodium infection reduced both the replication-competent virus pool in resting CD4+ T cells and the integrated virus DNA (iDNA) load in peripheral blood mononuclear cells in the monkeys. This reduction might be attributable to malaria-mediated activation and apoptotic induction of memory CD4+ T cells. Further studies indicated that histone acetylation and NF-kappaB (NF-κB) activation in resting CD4+ T cells may also play an important role in this reduction.

Conclusions: The findings of this work expand our knowledge of the interaction between these two diseases. As more HIV-1-infected individuals in malaria-endemic areas receive ART, we should explore whether any of the patients co-infected with Plasmodium experience virologic benefits.

Show MeSH
Related in: MedlinePlus