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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

Flow cytometric quantitation of the histone acetylation levels in lymphocytes from different phases in the two groups of monkeys. (A) Lymphocytes gated by size on a forward scatter vs. side scatter plot. (B) Two monkeys were selected from different groups for representative flow cytometric analyses of different histone acetylation levels. The acetylated histone levels of the gated cells were analyzed by measuring the fluorescence intensity of these cells. The figure presents the difference in the lymphocytes’ acetylation levels in the different groups at week 54 (5 weeks after Pc infection). (C) Higher histone acetylation levels were observed in lymphocytes in the ART + Pc group during Pc infection (MFI of 188.90 ± 51.33 at week 54 vs. 125.96 ± 20.80 at week 57). MFI values from weeks 54 and 57 in the same group were combined to examine the difference in acetylated histone levels between the two groups during the malaria phase. The Mann–Whitney U test was utilized for statistical analyses. The data are shown as the mean ± SD.
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Fig5: Flow cytometric quantitation of the histone acetylation levels in lymphocytes from different phases in the two groups of monkeys. (A) Lymphocytes gated by size on a forward scatter vs. side scatter plot. (B) Two monkeys were selected from different groups for representative flow cytometric analyses of different histone acetylation levels. The acetylated histone levels of the gated cells were analyzed by measuring the fluorescence intensity of these cells. The figure presents the difference in the lymphocytes’ acetylation levels in the different groups at week 54 (5 weeks after Pc infection). (C) Higher histone acetylation levels were observed in lymphocytes in the ART + Pc group during Pc infection (MFI of 188.90 ± 51.33 at week 54 vs. 125.96 ± 20.80 at week 57). MFI values from weeks 54 and 57 in the same group were combined to examine the difference in acetylated histone levels between the two groups during the malaria phase. The Mann–Whitney U test was utilized for statistical analyses. The data are shown as the mean ± SD.

Mentions: Previous studies showed that histone acetylation in resting CD4+ T cells could induce reservoir purging [24,25]. We thus examined the histone acetylation levels in peripheral blood lymphocytes (PBLs) in the monkeys during different phases. The results showed that the levels of global histone acetylation in PBLs, as measured based on mean fluorescence intensity (MFI), were much higher in the ART + Pc group during Pc infection than the levels in the ART group (MFI of 188.90 vs. 125.96; P = 0.001; Figure 5A–C).Figure 5


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)

Flow cytometric quantitation of the histone acetylation levels in lymphocytes from different phases in the two groups of monkeys. (A) Lymphocytes gated by size on a forward scatter vs. side scatter plot. (B) Two monkeys were selected from different groups for representative flow cytometric analyses of different histone acetylation levels. The acetylated histone levels of the gated cells were analyzed by measuring the fluorescence intensity of these cells. The figure presents the difference in the lymphocytes’ acetylation levels in the different groups at week 54 (5 weeks after Pc infection). (C) Higher histone acetylation levels were observed in lymphocytes in the ART + Pc group during Pc infection (MFI of 188.90 ± 51.33 at week 54 vs. 125.96 ± 20.80 at week 57). MFI values from weeks 54 and 57 in the same group were combined to examine the difference in acetylated histone levels between the two groups during the malaria phase. The Mann–Whitney U test was utilized for statistical analyses. The data are shown as the mean ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4269176&req=5

Fig5: Flow cytometric quantitation of the histone acetylation levels in lymphocytes from different phases in the two groups of monkeys. (A) Lymphocytes gated by size on a forward scatter vs. side scatter plot. (B) Two monkeys were selected from different groups for representative flow cytometric analyses of different histone acetylation levels. The acetylated histone levels of the gated cells were analyzed by measuring the fluorescence intensity of these cells. The figure presents the difference in the lymphocytes’ acetylation levels in the different groups at week 54 (5 weeks after Pc infection). (C) Higher histone acetylation levels were observed in lymphocytes in the ART + Pc group during Pc infection (MFI of 188.90 ± 51.33 at week 54 vs. 125.96 ± 20.80 at week 57). MFI values from weeks 54 and 57 in the same group were combined to examine the difference in acetylated histone levels between the two groups during the malaria phase. The Mann–Whitney U test was utilized for statistical analyses. The data are shown as the mean ± SD.
Mentions: Previous studies showed that histone acetylation in resting CD4+ T cells could induce reservoir purging [24,25]. We thus examined the histone acetylation levels in peripheral blood lymphocytes (PBLs) in the monkeys during different phases. The results showed that the levels of global histone acetylation in PBLs, as measured based on mean fluorescence intensity (MFI), were much higher in the ART + Pc group during Pc infection than the levels in the ART group (MFI of 188.90 vs. 125.96; P = 0.001; Figure 5A–C).Figure 5

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