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| 2. |
- Borggren, Marie, et al.
(författare)
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Increased Sensitivity to Broadly Neutralizing Antibodies of End-Stage Disease R5 HIV-1 Correlates with Evolution in Env Glycosylation and Charge.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Induction of broadly neutralizing antibodies, such as the monoclonal antibodies IgGb12, 2F5 and 2G12, is the objective of most antibody-based HIV-1 vaccine undertakings. However, despite the relative conserved nature of epitopes targeted by these antibodies, mechanisms underlying the sensitivity of circulating HIV-1 variants to broadly neutralizing antibodies are not fully understood. Here we have studied sensitivity to broadly neutralizing antibodies of HIV-1 variants that emerge during disease progression in relation to molecular alterations in the viral envelope glycoproteins (Env), using a panel of primary R5 HIV-1 isolates sequentially obtained before and after AIDS onset.
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| 3. |
- Casper, C, et al.
(författare)
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Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes
- 2002
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 18:5, s. 343-352
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Tidskriftsartikel (refereegranskat)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.
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| 4. |
- Casper, C, et al.
(författare)
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Coreceptor usage of primary HIV type 1 isolates obtained from different lymph node subsets
- 2005
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 21:12, s. 1003-1010
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Tidskriftsartikel (refereegranskat)abstract
- Biological characteristics of virus quantitatively rescued from different cell types present in lymph nodes of HIV-1-infected individuals in various stages of their disease were determined, not including patients with AIDS defining illness. Viruses were obtained by cocultivation with donor monocyte-derived macrophages and T-lymphocytes and their biological phenotype compared to viruses obtained from the peripheral blood mononuclear cells of the same patient. The biological phenotype was determined on established cell lines (U937-2, CEM, and MT-2) and on the U87.CD4 coreceptor indicator cell lines and variable region 3 (V3) of the envelope was subjected to direct sequencing. All isolates obtained from lymph node subsets used CCR5 as coreceptor. Furthermore, these viruses were also sensitive to inhibition by beta-chemokines as analyzed for viruses of one patient. All 12 V3 regions showed a unique sequence indicating compartmentalization within each patient. The biological phenotype of CCR5-dependent (R5) HIV-1 isolates obtained from PBMC resembles the phenotype of viruses isolated from different lymph node cell subsets.
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| 5. |
- Casper, CHE, et al.
(författare)
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Link between the X4 phenotype in human immunodeficiency virus type 1-infected mothers and their children, despite the early presence of R5 in the child
- 2002
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 186:7, s. 914-921
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Tidskriftsartikel (refereegranskat)abstract
- Coreceptor use was determined for human immunodeficiency virus type 1 (HIV-1) isolates of various subtypes from 11 women during pregnancy and their infected children. Isolates from peripheral blood mononuclear cells (n = 79) and from plasma (n = 59) were available. The clinical and immunological stages of HIV-1 infection were recorded. Coreceptor use was tested on human cell lines expressing CD4 and different chemokine receptors. The R5 virus predominated, and only 9 isolates from 2 mothers used CXC chemokine receptor 4. All children carried the R5 virus at the time of diagnosis of HIV-1 infection. In 2 children of mothers carrying the X4 virus, the virus switched from R5 to X4 or to R5X4 by age 18 months (child no. 9) and age 48 months (child no. 10), whereas no children followed up to a similar age whose mothers were carrying the R5 virus experienced such a switch (). This points to a link between the P = .048 presence of X4 virus in the mother and the emergence of X4 virus in her child.
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| 6. |
- Clevestig, P, et al.
(författare)
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The X4 phenotype of HIV type 1 evolves from R5 in two children of mothers, carrying X4, and is not linked to transmission
- 2005
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 21:5, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we found that emergence of the X4 viral phenotype in HIV-1-infected children was related to the presence of X4 in their mothers (C. H. Casper et al., J Infect Dis 2002; 186: 914-921). Here, we investigated the origin of the X4 phenotype in the child, analyzing two mother-child pairs (Ma-Ca, Mb-Cb) where the mothers carried X4 and their children developed X4 after an initial presence of R5. We used nested polymerase chain reaction of the env V3 region to generate 203 HIV-1 clones for sequencing (Ma, n = 44; Ca, n = 73; Mb, n = 61; Cb, n = 25) from DNA of peripheral blood mononuclear cell (PBMC) lysates, altogether 167 clones, or from cDNA of plasma RNA, 36 clones. PBMC and plasma isolate sequences from each time point enabled us to assign the probable phenotype to clone sequences in a phylogenetic tree. The transmission and evolution were reconstructed using the maximum likelihood method. In mother-child pair Ma-Ca, one maternal R5 isolate clustered with the child's R5 sequences, at the earliest time when R5 was isolated in the child, confirming this as a likely source of the transmitted R5 phenotype. At age 3, an X4 population was present in the child that had evolved from the child's own R5-associated population, clearly distinct from the maternal X4 sequences. The second mother-child pair (Mb-Cb) displayed a similar pattern. Amino acid substitution patterns corroborated the conclusions from the phylogenetic tree. Thus, in both children, the X4 virus developed from their own R5 population, and was not caused by transmission of X4.
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| 7. |
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| 8. |
- Esbjörnsson, Joakim, et al.
(författare)
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Increased survival among HIV-1 and HIV-2 dual-infected individuals compared to HIV-1 single-infected individuals
- 2014
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Ingår i: AIDS. - 1473-5571. ; 28:7, s. 949-957
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare survival times of HIV-1 single and HIV-1 and HIV-2 dual-infected individuals. Design: Prospective open cohort study. Methods: We analysed data from 259 HIV-1-seroincident cases (either HIV-1 single or HIV-1 and HIV-2 dual-infected) from a cohort with long follow-up (similar to 20 years) in order to study the influence of type of infection and infection order on mortality. Sex and age at HIV-1 infection date was controlled for in a Cox proportional-hazards model. Results: Dual-infected individuals had a 42% longer time from HIV-1 infection to death compared with single-infected individuals, adjusting for age asymmetries between groups. Dual-infected individuals with an HIV-2 infection preceding the HIV-1 infection had a more than two-fold lower mortality risk during follow-up than HIV-1 single-infected individuals. Conclusion: Survival time is longer and the risk of progression to death is lower among HIV-1 and HIV-2 dual-infected individuals compared to HIV-1 single-infected individuals. This natural inhibition could have implications for the development of future HIV-1 vaccines and therapeutics.
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| 9. |
- Esbjörnsson, Joakim, et al.
(författare)
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Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection.
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:3, s. 224-232
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood. METHODS: We analyzed data from 223 participants who were infected with HIV-1 after enrollment (with either HIV-1 infection alone or HIV-1 and HIV-2 infection) in a cohort with a long follow-up duration (approximately 20 years), according to whether HIV-2 infection occurred first, the time to the development of AIDS (time to AIDS), CD4+ and CD8+ T-cell counts, and measures of viral evolution. RESULTS: The median time to AIDS was 104 months (95% confidence interval [CI], 75 to 133) in participants with dual infection and 68 months (95% CI, 60 to 76) in participants infected with HIV-1 only (P=0.003). CD4+ T-cell levels were higher and CD8+ T-cell levels increased at a lower rate among participants with dual infection, reflecting slower disease progression. Participants with dual infection with HIV-2 infection preceding HIV-1 infection had the longest time to AIDS and highest levels of CD4+ T-cell counts. HIV-1 genetic diversity was significantly lower in participants with dual infections than in those with HIV-1 infection alone at similar time points after infection. CONCLUSIONS: Our results suggest that HIV-1 disease progression is inhibited by concomitant HIV-2 infection and that dual infection is associated with slower disease progression. The slower rate of disease progression was most evident in participants with dual infection in whom HIV-2 infection preceded HIV-1 infection. These findings could have implications for the development of HIV-1 vaccines and therapeutics. (Funded by the Swedish International Development Cooperation Agency-Swedish Agency for Research Cooperation with Developing Countries and others.).
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| 10. |
- Fenyö, Eva Maria, et al.
(författare)
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Human immunodeficiency virus type 1 biological variation and coreceptor use: from concept to clinical significance.
- 2011
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 270, s. 520-531
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Tidskriftsartikel (refereegranskat)abstract
- There is ample evidence for intra-patient evolution of the human immunodeficiency virus type 1 (HIV-1) biological phenotype during the pathogenic process. Evolution often involves switch of coreceptor use from CCR5 to CXCR4, but change to more flexible use of CCR5 occurs over time even in patients with maintained CCR5 use. The increasing use of entry inhibitors in the clinic, often specific for one or the other HIV-1 coreceptor or with different binding properties to CCR5, calls for virus testing in patients prior to treatment initiation. Cell lines expressing CCR5/CXCR4 chimeric receptors are tools for testing viruses for mode of CCR5 use. It is conceivable that small-molecule entry inhibitors that differentially bind to CCR5 can be matched for best effect against HIV-1 with different modes of CCR5 use, thereby allowing an individualized drug choice specifically tailored for each patient.
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