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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

The impact of Pc infection on the SIV reservoir. (A) A significantly reduced frequency of resting CD4+ T cells harboring replication-competent SIV was observed during malaria infection in the ART + Pc group. Four of 6 monkeys in the ART + Pc group maintained less than 0.51 IUPM during the malaria phase, whereas all 6 monkeys in the ART group maintained an IUPM value above or equal to 0.51. The IUPM values in the two groups of monkeys were significantly different during the malaria phase. (B) The fitted curve revealed dynamic changes in IUPM in the two groups during the study. Each arrow has the same meaning as indicated in Figure 1. (C) Dynamic plots of iDNA in PBMCs at each time point. The copy number was significantly reduced after Pc infection in the ART + Pc group (under ART) compared with the ART group (1.11 ± 6.76 vs. 0.23 ± 10.05 copies/105 PBMCs). The meaning of each arrow is the same as indicated in Figure 1. Fisher’s exact test was utilized to examine the difference in IUPM between the two monkey groups. The numbers of SIV iDNA copies at weeks 51, 54 and 73 in the PBMCs of monkeys in the same group were combined to examine the differences between the two groups. The Mann–Whitney U test was utilized. Empower (R) (www.empowerstats.com, X&Y Solutions, Inc., Boston, MA) and R (http://www.R-project.org) were used for smooth curve fitting.
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Fig2: The impact of Pc infection on the SIV reservoir. (A) A significantly reduced frequency of resting CD4+ T cells harboring replication-competent SIV was observed during malaria infection in the ART + Pc group. Four of 6 monkeys in the ART + Pc group maintained less than 0.51 IUPM during the malaria phase, whereas all 6 monkeys in the ART group maintained an IUPM value above or equal to 0.51. The IUPM values in the two groups of monkeys were significantly different during the malaria phase. (B) The fitted curve revealed dynamic changes in IUPM in the two groups during the study. Each arrow has the same meaning as indicated in Figure 1. (C) Dynamic plots of iDNA in PBMCs at each time point. The copy number was significantly reduced after Pc infection in the ART + Pc group (under ART) compared with the ART group (1.11 ± 6.76 vs. 0.23 ± 10.05 copies/105 PBMCs). The meaning of each arrow is the same as indicated in Figure 1. Fisher’s exact test was utilized to examine the difference in IUPM between the two monkey groups. The numbers of SIV iDNA copies at weeks 51, 54 and 73 in the PBMCs of monkeys in the same group were combined to examine the differences between the two groups. The Mann–Whitney U test was utilized. Empower (R) (www.empowerstats.com, X&Y Solutions, Inc., Boston, MA) and R (http://www.R-project.org) were used for smooth curve fitting.

Mentions: Pc infection significantly decreased the frequency of resting CD4+ T cells harboring replication-competent virus (defined as infectious units per million cells, or IUPM) (Figure 2A and B, Table 1). After the malaria was treated, the IUPM in the ART + Pc group remained significantly lower at weeks 68 and 73 compared with the IUPM in the ART group before ART was terminated (“No-malaria phase,” as shown in Figure 1; P = 0.001; Figure 2B). The ART + Pc group also showed a lower iDNA load in PBMCs after Pc infection (under ART) compared with the load in the ART group (means of 0.23 and 1.11 copies per 105 PBMCs, respectively; P = 0.047; Figure 2C). These results suggested that under ART, Pc infection decreased the viral reservoirs in SIV-infected macaques.Figure 2


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)

The impact of Pc infection on the SIV reservoir. (A) A significantly reduced frequency of resting CD4+ T cells harboring replication-competent SIV was observed during malaria infection in the ART + Pc group. Four of 6 monkeys in the ART + Pc group maintained less than 0.51 IUPM during the malaria phase, whereas all 6 monkeys in the ART group maintained an IUPM value above or equal to 0.51. The IUPM values in the two groups of monkeys were significantly different during the malaria phase. (B) The fitted curve revealed dynamic changes in IUPM in the two groups during the study. Each arrow has the same meaning as indicated in Figure 1. (C) Dynamic plots of iDNA in PBMCs at each time point. The copy number was significantly reduced after Pc infection in the ART + Pc group (under ART) compared with the ART group (1.11 ± 6.76 vs. 0.23 ± 10.05 copies/105 PBMCs). The meaning of each arrow is the same as indicated in Figure 1. Fisher’s exact test was utilized to examine the difference in IUPM between the two monkey groups. The numbers of SIV iDNA copies at weeks 51, 54 and 73 in the PBMCs of monkeys in the same group were combined to examine the differences between the two groups. The Mann–Whitney U test was utilized. Empower (R) (www.empowerstats.com, X&Y Solutions, Inc., Boston, MA) and R (http://www.R-project.org) were used for smooth curve fitting.
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Related In: Results  -  Collection

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Fig2: The impact of Pc infection on the SIV reservoir. (A) A significantly reduced frequency of resting CD4+ T cells harboring replication-competent SIV was observed during malaria infection in the ART + Pc group. Four of 6 monkeys in the ART + Pc group maintained less than 0.51 IUPM during the malaria phase, whereas all 6 monkeys in the ART group maintained an IUPM value above or equal to 0.51. The IUPM values in the two groups of monkeys were significantly different during the malaria phase. (B) The fitted curve revealed dynamic changes in IUPM in the two groups during the study. Each arrow has the same meaning as indicated in Figure 1. (C) Dynamic plots of iDNA in PBMCs at each time point. The copy number was significantly reduced after Pc infection in the ART + Pc group (under ART) compared with the ART group (1.11 ± 6.76 vs. 0.23 ± 10.05 copies/105 PBMCs). The meaning of each arrow is the same as indicated in Figure 1. Fisher’s exact test was utilized to examine the difference in IUPM between the two monkey groups. The numbers of SIV iDNA copies at weeks 51, 54 and 73 in the PBMCs of monkeys in the same group were combined to examine the differences between the two groups. The Mann–Whitney U test was utilized. Empower (R) (www.empowerstats.com, X&Y Solutions, Inc., Boston, MA) and R (http://www.R-project.org) were used for smooth curve fitting.
Mentions: Pc infection significantly decreased the frequency of resting CD4+ T cells harboring replication-competent virus (defined as infectious units per million cells, or IUPM) (Figure 2A and B, Table 1). After the malaria was treated, the IUPM in the ART + Pc group remained significantly lower at weeks 68 and 73 compared with the IUPM in the ART group before ART was terminated (“No-malaria phase,” as shown in Figure 1; P = 0.001; Figure 2B). The ART + Pc group also showed a lower iDNA load in PBMCs after Pc infection (under ART) compared with the load in the ART group (means of 0.23 and 1.11 copies per 105 PBMCs, respectively; P = 0.047; Figure 2C). These results suggested that under ART, Pc infection decreased the viral reservoirs in SIV-infected macaques.Figure 2

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