10 research outputs found

    Two types of cytotoxic lymphocyte regulation explain kinetics of immune response to human immunodeficiency virus

    No full text
    The organization of the cytotoxic T lymphocyte (CTL) response at organismal level is poorly understood. We propose a mathematical model describing the interaction between HIV and its host that explains 20 quantitative observations made in HIV-infected individuals and simian immunodeficiency virus-infected monkeys, including acute infection and response to various antiretroviral therapy regimens. The model is built on two modes of CTL activation: direct activation by infected cells and indirect activation by CD4 helper cells activated by small amounts of virus. Effective infection of helper cells by virus leads to a stable chronic infection at high virus load. We assume that CTLs control virus by killing infected cells. We explain the lack of correlation between the CTL number and the virus decay rate in therapy and predict that individuals with a high virus load can be switched to a low-viremia state that will maintain stability after therapy, but the switch requires fine adjustment of therapy regimen based on the model and individual parameters

    An anti-CD45RO immunotoxin kills HIV-latently infected cells from individuals on HAART with little effect on CD8 memory

    No full text
    CD4(+) CD45RO(+) T cells are the major latent viral reservoir in HIV-infected individuals and hence a major obstacle in curing the disease. An anti-CD45RO immunotoxin (IT) can decrease the number of both productively and latently infected CD4(+) T cells obtained from HIV-infected individuals with detectable viremia. In this study, we determined whether this IT could also kill latently infected replication-competent CD4(+) T cells obtained from infected individuals without detectable plasma viremia. Our results demonstrate that ex vivo treatment with the anti-CD45RO IT significantly reduced the frequency of these cells. In contrast, the IT had only a modest effect on the cytomegalalovirus-specific memory responses of CD8(+) T cells. These results suggest that purging latent cells from infected individuals on highly active antiretroviral therapy with the anti-CD45RO IT might reduce the HIV latent reservoir without seriously compromising CD8(+) T cell memory responses

    Genotyping-by-sequencing supports a genetic basis for wing reduction in an alpine New Zealand stonefly

    Get PDF
    Wing polymorphism is a prominent feature of numerous insect groups, but the genomic basis for this diversity remains poorly understood. Wing reduction is a commonly observed trait in many species of stonefies, particularly in cold or alpine environments. The widespread New Zealand stonefy Zelandoperla fenestrata species group (Z. fenestrata, Z. tillyardi, Z. pennulata) contains populations ranging from fully winged (macropterous) to vestigial-winged (micropterous), with the latter phenotype typically associated with high altitudes. The presence of fightless forms on numerous mountain ranges, separated by lowland fully winged populations, suggests wing reduction has occurred multiple times. We use Genotyping by Sequencing (GBS) to test for genetic diferentiation between fully winged (n=62) and vestigial-winged (n=34) individuals, sampled from a sympatric population of distinct wing morphotypes, to test for a genetic basis for wing morphology. While we found no population genetic diferentiation between these two morphotypes across 6,843 SNP loci, we did detect several outlier loci that strongly diferentiated morphotypes across independent tests. These fndings indicate that small regions of the genome are likely to be highly diferentiated between morphotypes, suggesting a genetic basis for wing reduction. Our results provide a clear basis for ongoing genomic analysis to elucidate critical regulatory pathways for wing development in Pterygota
    corecore