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Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes

Casper, C; Naver, L; Clevestig, P; Belfrage, E; Leitner, T; Albert, J; Lindgren, S; Ottenblad, C; Bohlin, AB and Fenyö, Eva Maria LU , et al. (2002) In AIDS Research and Human Retroviruses 18(5). p.343-352
Abstract
Change of HIV-1 coreceptor use has been connected to progression of disease in children infected with HIV-1, presumably subtype B. It has not been possible to discern whether the appearance of new viral phenotypes precedes disease development or comes as a consequence of it. We studied the evolution of coreceptor use in HIV-1 isolates from 24 vertically infected children. Their clinical, virological, and immunological status was recorded and the env V3 subtype was determined by DNA sequencing. Coreceptor use was tested on human cell lines, expressing CD4 together with CCR5, CXCR4, and other chemokine receptors. The children carried five different env subtypes (nine A, five B, four C, three D, and one G) and one circulating recombinant... (More)
Change of HIV-1 coreceptor use has been connected to progression of disease in children infected with HIV-1, presumably subtype B. It has not been possible to discern whether the appearance of new viral phenotypes precedes disease development or comes as a consequence of it. We studied the evolution of coreceptor use in HIV-1 isolates from 24 vertically infected children. Their clinical, virological, and immunological status was recorded and the env V3 subtype was determined by DNA sequencing. Coreceptor use was tested on human cell lines, expressing CD4 together with CCR5, CXCR4, and other chemokine receptors. The children carried five different env subtypes (nine A, five B, four C, three D, and one G) and one circulating recombinant form, CRF01_AE (n=2). Of the 143 isolates, 86 originated from peripheral blood mononuclear cells (PBMCs) and 57 originated from plasma, received at 90 time points. In 52 of 54 paired plasma and PBMC isolates the coreceptor use was concordant. All 74 isolates obtained at 41 time points during the first year of life used CCR5. A change from use of CCR5 to use of CXCR4 occurred in four children infected with subtype A, D, or CRF01_AE after they had reached 1.5 to 5.8 years of age. There was a significant association with decreased CD4 1 cell levels and severity of disease but, interestingly, the coreceptor change appeared months or even years after the beginning of the immunological deterioration. Thus CXCR4-using virus may emerge as a possible consequence of immune deficiency. The results provide new insights into AIDS development in children. (Less)
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in
AIDS Research and Human Retroviruses
volume
18
issue
5
pages
343 - 352
publisher
Mary Ann Liebert, Inc.
external identifiers
  • wos:000174422300005
  • pmid:11897036
  • scopus:0036201825
ISSN
1931-8405
DOI
10.1089/088922202753519124
language
English
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yes
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2856a59c-e6be-4fee-952c-ce41082d6242 (old id 342151)
date added to LUP
2007-08-13 14:26:52
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2017-01-22 03:29:08
@article{2856a59c-e6be-4fee-952c-ce41082d6242,
  abstract     = {Change of HIV-1 coreceptor use has been connected to progression of disease in children infected with HIV-1, presumably subtype B. It has not been possible to discern whether the appearance of new viral phenotypes precedes disease development or comes as a consequence of it. We studied the evolution of coreceptor use in HIV-1 isolates from 24 vertically infected children. Their clinical, virological, and immunological status was recorded and the env V3 subtype was determined by DNA sequencing. Coreceptor use was tested on human cell lines, expressing CD4 together with CCR5, CXCR4, and other chemokine receptors. The children carried five different env subtypes (nine A, five B, four C, three D, and one G) and one circulating recombinant form, CRF01_AE (n=2). Of the 143 isolates, 86 originated from peripheral blood mononuclear cells (PBMCs) and 57 originated from plasma, received at 90 time points. In 52 of 54 paired plasma and PBMC isolates the coreceptor use was concordant. All 74 isolates obtained at 41 time points during the first year of life used CCR5. A change from use of CCR5 to use of CXCR4 occurred in four children infected with subtype A, D, or CRF01_AE after they had reached 1.5 to 5.8 years of age. There was a significant association with decreased CD4 1 cell levels and severity of disease but, interestingly, the coreceptor change appeared months or even years after the beginning of the immunological deterioration. Thus CXCR4-using virus may emerge as a possible consequence of immune deficiency. The results provide new insights into AIDS development in children.},
  author       = {Casper, C and Naver, L and Clevestig, P and Belfrage, E and Leitner, T and Albert, J and Lindgren, S and Ottenblad, C and Bohlin, AB and Fenyö, Eva Maria and Ehrnst, A},
  issn         = {1931-8405},
  language     = {eng},
  number       = {5},
  pages        = {343--352},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {AIDS Research and Human Retroviruses},
  title        = {Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes},
  url          = {http://dx.doi.org/10.1089/088922202753519124},
  volume       = {18},
  year         = {2002},
}