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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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Phylogenetic tree based on the V1-V2 fragment of the HIV-1 env gene nucleotide sequences. Phylogenetic tree to assess if the HIV-1 genome of children with severe anaemia (cases, Hb<5.0 g/dL) is different from those without severe anaemia (controls). Subtype A and CRF-13 reference sequences are used as outgroup sequence.
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Figure 2: Phylogenetic tree based on the V1-V2 fragment of the HIV-1 env gene nucleotide sequences. Phylogenetic tree to assess if the HIV-1 genome of children with severe anaemia (cases, Hb<5.0 g/dL) is different from those without severe anaemia (controls). Subtype A and CRF-13 reference sequences are used as outgroup sequence.

Mentions: Phylogenetic analysis of V1-V2 nucleotide sequences showed that 57 of 58 isolates clustered with subtype C reference sequences (bootstrap value: 99%, Figure 2). Only one child, a child recruited as control, had a new circulating recombinant form that showed similarity with CRF13-cpx, which has genomic regions identified as subtypes A, G, and J [46].


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)

Phylogenetic tree based on the V1-V2 fragment of the HIV-1 env gene nucleotide sequences. Phylogenetic tree to assess if the HIV-1 genome of children with severe anaemia (cases, Hb<5.0 g/dL) is different from those without severe anaemia (controls). Subtype A and CRF-13 reference sequences are used as outgroup sequence.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Phylogenetic tree based on the V1-V2 fragment of the HIV-1 env gene nucleotide sequences. Phylogenetic tree to assess if the HIV-1 genome of children with severe anaemia (cases, Hb<5.0 g/dL) is different from those without severe anaemia (controls). Subtype A and CRF-13 reference sequences are used as outgroup sequence.
Mentions: Phylogenetic analysis of V1-V2 nucleotide sequences showed that 57 of 58 isolates clustered with subtype C reference sequences (bootstrap value: 99%, Figure 2). Only one child, a child recruited as control, had a new circulating recombinant form that showed similarity with CRF13-cpx, which has genomic regions identified as subtypes A, G, and J [46].

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