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Severe anaemia is not associated with HIV-1 env gene characteristics in Malawian children.

Calis JC, Rotteveel HP, van der Kuyl AC, Zorgdrager F, Kachala D, van Hensbroek MB, Cornelissen M - BMC Infect. Dis. (2008)

Bottom Line: In vitro studies have suggested that specific HIV strains, like X4 that uses the CXCR4 co-receptor present on erythroid precursors, are associated with diminished erythropoiesis.All V1-V2-V3 characteristics tested: V3 charge, V1-V2 length and potential glycosylation sites, were not found to be different between cases and controls.The prevalence of X4 strains in these young HIV-1-subtype-C-infected children that were most likely vertically infected and naïve to anti-retroviral therapy can be considered high compared to previous results from Malawi.

View Article: PubMed Central - HTML - PubMed

Affiliation: Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands. Job.Calis@gmail.com

ABSTRACT

Background: Anaemia is the most common haematological complication of HIV and associated with a high morbidity and a poor prognosis. The pathogenesis of HIV-associated anaemia is poorly understood and may include a direct effect of HIV on erythropoiesis. In vitro studies have suggested that specific HIV strains, like X4 that uses the CXCR4 co-receptor present on erythroid precursors, are associated with diminished erythropoiesis. This co-receptor affinity is determined by changes in the hypervariable loop of the HIV-1 envelope genome. In a previous case-control study we observed an association between HIV and severe anaemia in Malawian children that could not be fully explained by secondary infections and micronutrient deficiencies alone. We therefore explored the possibility that alterations in the V1-V2-V3 fragment of HIV-1 were associated with severe anaemia.

Methods: Using peripheral blood nucleic acid isolates of HIV-infected children identified in the previous studied we assessed if variability of the V1-V2-V3 region of HIV and the occurrence of X4 strains were more common in HIV-infected children with (cases, n = 29) and without severe anaemia (controls, n = 30). For 15 cases bone marrow isolates were available to compare against peripheral blood. All children were followed for 18 months after recruitment.

Results: Phylogenetic analysis showed that HIV-1 subtype C was present in all but one child. All V1-V2-V3 characteristics tested: V3 charge, V1-V2 length and potential glycosylation sites, were not found to be different between cases and controls. Using a computer model (C-PSSM) four children (7.8%) were identified to have an X4 strain. This prevalence was not different between study groups (p = 1.00). The V3 loop characteristics for bone marrow and peripheral blood isolates in the case group were identical. None of the children identified as having an X4 strain developed a (new) episode of severe anaemia during follow up.

Conclusion: The prevalence of X4 strains in these young HIV-1-subtype-C-infected children that were most likely vertically infected and naïve to anti-retroviral therapy can be considered high compared to previous results from Malawi. It is unlikely that V1-V2-V3 fragment characteristics and HIV co-receptor affinity is an important feature in the development of severe anaemia in Malawian children.

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Distribution of potential N-linked glycosylation sites on V1-V2-V3 per study group. Distribution of number of potential N-linked glycosylation sites on the V1-V2-V3 fragment in children with severe anaemia (cases, Hb<5.0 g/dL) as compared to those without severe anaemia (controls). The distribution is expressed as a percentage of the total number of fragments analysed per study group (Controls: n = 25, Cases n = 26). Error bars express 95%. p = 0.75.
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Figure 5: Distribution of potential N-linked glycosylation sites on V1-V2-V3 per study group. Distribution of number of potential N-linked glycosylation sites on the V1-V2-V3 fragment in children with severe anaemia (cases, Hb<5.0 g/dL) as compared to those without severe anaemia (controls). The distribution is expressed as a percentage of the total number of fragments analysed per study group (Controls: n = 25, Cases n = 26). Error bars express 95%. p = 0.75.

Mentions: All isolates contained one potential N-linked glycosylation site in the V3 loop. The number of potential glycosylation sites on the V1-V3 fragment ranged between 10 and 17 (Figure 5) and was not different amongst cases and controls (p = 0.75).


Severe anaemia is not associated with HIV-1 env gene characteristics in Malawian children.

Calis JC, Rotteveel HP, van der Kuyl AC, Zorgdrager F, Kachala D, van Hensbroek MB, Cornelissen M - BMC Infect. Dis. (2008)

Distribution of potential N-linked glycosylation sites on V1-V2-V3 per study group. Distribution of number of potential N-linked glycosylation sites on the V1-V2-V3 fragment in children with severe anaemia (cases, Hb<5.0 g/dL) as compared to those without severe anaemia (controls). The distribution is expressed as a percentage of the total number of fragments analysed per study group (Controls: n = 25, Cases n = 26). Error bars express 95%. p = 0.75.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2311312&req=5

Figure 5: Distribution of potential N-linked glycosylation sites on V1-V2-V3 per study group. Distribution of number of potential N-linked glycosylation sites on the V1-V2-V3 fragment in children with severe anaemia (cases, Hb<5.0 g/dL) as compared to those without severe anaemia (controls). The distribution is expressed as a percentage of the total number of fragments analysed per study group (Controls: n = 25, Cases n = 26). Error bars express 95%. p = 0.75.
Mentions: All isolates contained one potential N-linked glycosylation site in the V3 loop. The number of potential glycosylation sites on the V1-V3 fragment ranged between 10 and 17 (Figure 5) and was not different amongst cases and controls (p = 0.75).

Bottom Line: In vitro studies have suggested that specific HIV strains, like X4 that uses the CXCR4 co-receptor present on erythroid precursors, are associated with diminished erythropoiesis.All V1-V2-V3 characteristics tested: V3 charge, V1-V2 length and potential glycosylation sites, were not found to be different between cases and controls.The prevalence of X4 strains in these young HIV-1-subtype-C-infected children that were most likely vertically infected and naïve to anti-retroviral therapy can be considered high compared to previous results from Malawi.

View Article: PubMed Central - HTML - PubMed

Affiliation: Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands. Job.Calis@gmail.com

ABSTRACT

Background: Anaemia is the most common haematological complication of HIV and associated with a high morbidity and a poor prognosis. The pathogenesis of HIV-associated anaemia is poorly understood and may include a direct effect of HIV on erythropoiesis. In vitro studies have suggested that specific HIV strains, like X4 that uses the CXCR4 co-receptor present on erythroid precursors, are associated with diminished erythropoiesis. This co-receptor affinity is determined by changes in the hypervariable loop of the HIV-1 envelope genome. In a previous case-control study we observed an association between HIV and severe anaemia in Malawian children that could not be fully explained by secondary infections and micronutrient deficiencies alone. We therefore explored the possibility that alterations in the V1-V2-V3 fragment of HIV-1 were associated with severe anaemia.

Methods: Using peripheral blood nucleic acid isolates of HIV-infected children identified in the previous studied we assessed if variability of the V1-V2-V3 region of HIV and the occurrence of X4 strains were more common in HIV-infected children with (cases, n = 29) and without severe anaemia (controls, n = 30). For 15 cases bone marrow isolates were available to compare against peripheral blood. All children were followed for 18 months after recruitment.

Results: Phylogenetic analysis showed that HIV-1 subtype C was present in all but one child. All V1-V2-V3 characteristics tested: V3 charge, V1-V2 length and potential glycosylation sites, were not found to be different between cases and controls. Using a computer model (C-PSSM) four children (7.8%) were identified to have an X4 strain. This prevalence was not different between study groups (p = 1.00). The V3 loop characteristics for bone marrow and peripheral blood isolates in the case group were identical. None of the children identified as having an X4 strain developed a (new) episode of severe anaemia during follow up.

Conclusion: The prevalence of X4 strains in these young HIV-1-subtype-C-infected children that were most likely vertically infected and naïve to anti-retroviral therapy can be considered high compared to previous results from Malawi. It is unlikely that V1-V2-V3 fragment characteristics and HIV co-receptor affinity is an important feature in the development of severe anaemia in Malawian children.

Show MeSH
Related in: MedlinePlus