Počet záznamů: 1  

Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals

  1. 1.
    0475267 - ÚOCHB 2018 RIV GB eng J - Článek v odborném periodiku
    Weber, Jan - Gibson, R. M. - Sácká, Lenka - Strunin, Dmytro - Hodek, Jan - Weberová, Jitka - Pávová, Marcela - Alouani, D. J. - Asaad, R. - Rodriguez, B. - Lederman, M. M. - Quinones-Mateu, M. E.
    Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals.
    AIDS Research and Therapy. Roč. 14, Mar 20 (2017), č. článku 15. ISSN 1742-6405. E-ISSN 1742-6405
    Grant CEP: GA MŠMT(CZ) LK11207
    Institucionální podpora: RVO:61388963
    Klíčová slova: HIV-1 * replicative fitness * disease progression * viremic non-progressors
    Obor OECD: Virology
    Impakt faktor: 2.357, rok: 2017
    https://aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-017-0144-0

    Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals--termed viremic non-progressors (VNP) or controllers--do not seem to progress to AIDS, maintaining high CD4(+) T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients, however, limited work has been done to characterize viral factors in viremic controllers. We analyzed HIV-1 isolates from three VNP individuals and compared the replicative fitness, near full-length HIV-1 genomes and intra-patient HIV-1 genetic diversity with viruses from three typical (TP) and one rapid (RP) progressor individuals. Viremic non-progressors and typical patients were infected for > 10 years (range 10-17 years), with a mean CD4(+) T-cell count of 472 cells/mm(3) (442-529) and 400 cells/mm(3) (126-789), respectively. VNP individuals had a less marked decline in CD4(+) cells (mean -0.56, range -0.4 to -0.7 CD4(+)/month) than TP patients (mean -10.3, -8.2 to -13.1 CD4(+)/month). Interestingly, VNP individuals carried viruses with impaired replicative fitness, compared to HIV-1 isolates from the TP and RP patients (p < 0.05, 95% CI). Although analyses of the near full-length HIV-1 genomes showed no clear patterns of single-nucleotide polymorphisms (SNP) that could explain the decrease in replicative fitness, both the number of SNPs and HIV-1 population diversity correlated inversely with the replication capacity of the viruses (r = -0.956 and r = -0.878, p < 0.01, respectively). It is likely that complex multifactorial parameters govern HIV-1 disease progression in each individual, starting with the infecting virus (phenotype, load, and quasispecies diversity) and the intrinsic ability of the host to respond to the infection. Here we analyzed a subset of viremic controller patients and demonstrated that similar to the phenomenon observed in patients with a discordant response to antiretroviral therapy (i.e., high CD4(+) cell counts with detectable plasma HIV-1 RNA load), reduced viral replicative fitness seems to be linked to slow disease progression in these antiretroviral-naive individuals.
    Trvalý link: http://hdl.handle.net/11104/0272112

     
     
Počet záznamů: 1  

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