Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30

HIV-1-infected cells persist indefinitely despite the use of combination antiretroviral therapy (ART), and novel therapeutic strategies to target and purge residual infected cells in individuals on ART are urgently needed. Here, we demonstrate that CD4+ T cell-associated HIV-1 RNA is often highly enriched in cells expressing CD30, and that cells expressing this marker considerably contribute to the total pool of transcriptionally active CD4+ lymphocytes in individuals on suppressive ART. Using in situ RNA hybridization studies, we show co-localization of CD30 with HIV-1 transcriptional activity in gut-associated lymphoid tissues. We also demonstrate that ex vivo treatment with brentuximab vedotin, an antibody-drug conjugate (ADC) that targets CD30, significantly reduces the total amount of HIV-1 DNA in peripheral blood mononuclear cells obtained from infected, ART-suppressed individuals. Finally, we observed that an HIV-1-infected individual, who received repeated brentuximab vedotin infusions for lymphoma, had no detectable virus in peripheral blood mononuclear cells. Overall, CD30 may be a marker of residual, transcriptionally active HIV-1 infected cells in the setting of suppressive ART. Given that CD30 is only expressed on a small number of total mononuclear cells, it is a potential therapeutic target of persistent HIV-1 infection

Altimetry and transponder ground simulation experiment

We have designed and built a compact demonstrator unit for the investigation of altimetry and transponder applications. A small light-weight breadboard carries a compact frequency doubled Nd:YAG pulse laser, an afocal beam expansion optics, a small receiver telescope with spectral and spatial filter arrangements and a sensitive photo-detector. The output laser energy can be as high as 45 mJ with a pulse-width of 3 ns and the telescope aperture is 10 cm. Simulations [Degnan, J.J., 2006. Simulating interplanetary transponder and laser communications experiments via dual station ranging to SLR satellites. In: Proceedings of the 15th International Workshop on Laser Ranging, Canberra, Australia, pp. 457–462] suggested that the link margin for low Earth orbiting satellites (LEO) is comfortable. Successful satellite laser ranging from this dual-station experiment in several different configurations was achieved up to the MEO orbit in a 10 day provisional installation

Possible clearance of transfusion-acquired nef/LTR-deleted attenuated HIV-1 infection by an elite controller with CCR5 Delta 32 heterozygous and HLA-B57 genotype

Background: Subject C135 is one of the members of the Sydney Blood Bank Cohort, infected in 1981 through transfusion with attenuated nef/3′ long terminal repeat (LTR)-deleted HI V-1, and has maintained undetectable plasma viral load and steady CD4 cell count, in the absence of therapy. Uniquely, C135 combines five factors separately associated with control of viraemia: nef/LTR-deleted HI V-1, HLA -B57, HLA -DR13, heterozygous CCRccr5 Δ32 genotype and vigorous p24-stimulated peripheral blood mononuclear cell (PBMC) proliferation. Therefore, we studied in detail viral burden and immunological responses in this individual.Methods: PBMC and gut and lymph node biopsy samples were analysed for proviral HI V-1 DNA by real-time and nested PCR s, and nef/LTR alleles by nested PCR . HI V-specific antibodies were studied by Western blotting, and CD4+ and CD8+ T lymphocyte responses were measured by proliferation and cytokine production in vitro.Results: PBMC samples from 1996, but not since, showed amplification of nef alleles with gross deletions. Infectious HI V-1 was never recovered. Proviral HI V-1 DNA was not detected in recent PBMC or gut or lymph node biopsy samples. C135 has a consistently weak antibody response and a substantial CD4+ T cell proliferative response to a previously described HLA -DR13-restricted epitope of HI V-1 p24 in vitro, which augmented a CD8+ T cell response to an immunodominant HLA -B57-restricted epitope of p24, while his T cells show reduced levels of CCRccr5.Conclusions: Subject C135’s early PCR and weak antibody results are consistent with limited infection with a poorly replicating nef/LTR-deleted strain of HI V-1. With his HLA -B57-restricted gag-specific CD8 and helper HLA -DR13-restricted CD4 T cell proliferative responses, C135 appears to have cleared his HI V-1 infection 37 years after transfusion

CD32 expression is associated to T-cell activation and is not a marker of the HIV-1 reservoir

CD32 has been shown to be preferentially expressed in latently HIV-1-infected cells in an in vitro model of quiescent CD4 T cells. Here we show that stimulation of CD4+ T cells with IL-2, IL-7, PHA, and anti-CD3/CD28 antibodies induces T-cell proliferation, co-expression of CD32 and the activation of the markers HLA-DR and CD69. HIV-1 infection increases CD32 expression. 79.2% of the CD32+/CD4+ T cells from HIV+ individuals under antiretroviral treatment were HLA-DR+. Resting CD4+ T cells infected in vitro generally results in higher integration of provirus. We observe no difference in provirus integration or replication-competent inducible latent HIV-1 in CD32+ or CD32− CD4+ T cells from HIV+ individuals. Our results demonstrate that CD32 expression is a marker of CD4+ T cell activation in HIV+ individuals and raises questions regarding the immune resting status of CD32+ cells harboring HIV-1 proviruses. CD32 has been previously shown to be expressed preferentially by CD4 T cells latently harbouring HIV-1. Here the authors show that CD32 expression in CD4 T cells is associated with T cell activation, is up-regulated by HIV-1 infection and importantly does not appear to represent an enriched cellular niche for latent HIV-1