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  • 1
    Online Resource
    Online Resource
    A highly virulent variant of HIV-1 circulating in the Netherlands
    American Association for the Advancement of Science (AAAS) ; 2022
    In:  Science Vol. 375, No. 6580 ( 2022-02-04), p. 540-545
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 375, No. 6580 ( 2022-02-04), p. 540-545
    Abstract: A cluster of HIV-infected individuals with high viral loads, rapid CD4 + cell declines, and increased infectivity has been detected in Europe.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abk1688
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 2
    Online Resource
    Online Resource
    Robust Vaccine-Induced as Well as Hybrid B- and T-Cell Immunity across SARS-CoV-2 Vaccine Platforms in People with HIV
    American Society for Microbiology ; 2023
    In:  Microbiology Spectrum Vol. 11, No. 3 ( 2023-06-15)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 11, No. 3 ( 2023-06-15)
    Abstract: Few studies have comprehensively compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced and hybrid B- and T-cell responses in people with HIV (PWH) to those in comparable controls without HIV. We included 195 PWH and 246 comparable controls from the AGE h IV COVID-19 substudy. A positive nucleocapsid antibody (INgezim IgA/IgM/IgG) or self-reported PCR test defined prior SARS-CoV-2 infection. SARS-CoV-2 anti-spike (anti-S) IgG titers and anti-S IgG production by memory B cells were assessed. Neutralizing antibody titers were determined in a subset of participants. T-cell responses were assessed by gamma interferon (IFN-γ) release and activation-induced marker assay. We estimated mean differences in postvaccination immune responses (β) between levels of determinants. Anti-S IgG titers and anti-S IgG production by memory B cells were not different between PWH and controls. Prior SARS-CoV-2 infection (β = 0.77), receiving mRNA vaccine (β = 0.56), female sex (β = 0.24), fewer days between last vaccination and sampling (β = 0.07), and a CD4/CD8 ratio of 〈 1.0 (β = −0.39) were independently associated with anti-S IgG titers, but HIV status was not. Neutralization titers against the ancestral and Delta and Omicron SARS-CoV-2 variants were not different between PWH and controls. IFN-γ release was higher in PWH. Prior SARS-CoV-2 infection (β = 2.39), HIV-positive status (β = 1.61), and fewer days between last vaccination and sampling (β = 0.23) were independently associated with higher IFN-γ release. The percentages of SARS-CoV-2-reactive CD4 + and CD8 + T cells, however, were not different between PWH and controls. Individuals with well-controlled HIV generally mount robust vaccine-induced as well as hybrid B- and T-cell immunity across SARS-CoV-2 vaccine platforms similar to controls. Determinants of a reduced vaccine response were likewise largely similar in both groups and included a lower CD4/CD8 ratio. IMPORTANCE Some studies have suggested that people with HIV may respond less well to vaccines against SARS-CoV-2. We comprehensively compared B- and T-cell responses to different COVID-19 vaccines in middle-aged persons with well-treated HIV and individuals of the same age without HIV, who were also highly comparable in terms of demographics and lifestyle, including those with prior SARS-CoV-2 infection. Individuals with HIV generally mounted equally robust immunity to the different vaccines. Even stronger immunity was observed in both groups after prior SARS-CoV-2 infection. These findings are reassuring with respect to the efficacy of SARS-Cov-2 vaccines for the sizable and increasing global population of people with HIV with access and a good response to HIV treatment.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.01155-23
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2807133-5
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  • 3
    Online Resource
    Online Resource
    Table_1.XLSX
    Frontiers Media SA ; 2022
    In:  Frontiers in Microbiology Vol. 13 ( 2022-9-16)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-9-16)
    Abstract: Anelloviruses (AVs) are widespread in the population and infect humans at the early stage of life. The mode of transmission of AVs is still unknown, however, mother-to-child transmission, e.g., via breastfeeding, is one of the likely infection routes. To determine whether the mother-to-child transmission of AVs may still occur despite the absence of natural birth and breastfeeding, 29 serum samples from five HIV-1-positive mother and child pairs were Illumina-sequenced. The Illumina reads were mapped to an AV lineage database “Anellometrix” containing 502 distinct ORF1 sequences. Although the majority of lineages from the mother were not shared with the child, the mother and child anellomes did display a significant similarity. These findings suggest that AVs may be transmitted from mothers to their children via different routes than delivery or breastfeeding.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2022.951040
    DOI: 10.3389/fmicb.2022.951040.s001
    DOI: 10.3389/fmicb.2022.951040.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 4
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    Online Resource
    Cell-Associated HIV-1 Unspliced-to-Multiply-Spliced RNA Ratio at 12 Weeks of ART Predicts Immune Reconstitution on Therapy
    American Society for Microbiology ; 2021
    In:  mBio Vol. 12, No. 2 ( 2021-04-27)
    Details
    In: mBio, American Society for Microbiology, Vol. 12, No. 2 ( 2021-04-27)
    Abstract: Incomplete restoration of CD4 + T-cell counts on antiretroviral therapy (ART) is a major predictor of HIV-related morbidity and mortality. To understand the possible mechanisms behind this poor immunological response despite viral suppression, we longitudinally measured more than 50 virological and immunological biomarkers in a cohort of HIV-infected individuals at several time points during the first 96 weeks of virologically suppressive ART. No baseline virological or immunological marker was predictive of the degree of immune reconstitution. However, the cell-associated HIV-1 unspliced-to-multiply-spliced (US/MS) RNA ratio at 12 weeks of ART positively correlated with markers of CD4 + T-cell activation and apoptosis and negatively predicted both the absolute and relative CD4 + T-cell counts at 48 and 96 weeks. A higher US/MS RNA ratio may reflect the higher frequency of productively infected cells that could exert pressure on the immune system, contributing to persistent immune activation and apoptosis and subsequently to a poor immunological response to ART. IMPORTANCE Human immunodeficiency virus (HIV) infection is currently managed by antiretroviral drugs, which block virus replication and promote immune restoration. However, the latter effect is not universal, with a proportion of infected individuals failing to sufficiently reconstitute their immune function despite a successful virological response to antiretroviral therapy (ART). No reliable predictive markers of immunological failure have been identified, and there is still no efficient therapeutic strategy, apart from ART itself, to facilitate immune reconstitution. Here, we measured more than 50 viral and host biomarkers at five time points during the first 2 years of ART and identified the cell-associated HIV-1 unspliced-to-multiply-spliced RNA ratio at 12 weeks of ART as a predictive factor for the immunological response to therapy. Moreover, the same marker positively correlated with markers of CD4 + T-cell activation and apoptosis. The fact that a virological biomarker performed better than any immunological biomarker in predicting an immunological outcome highlights the importance of considering the residual HIV activity on ART as a correlate and a possible cause of the residual immune dysfunction that frequently occurs despite virologically suppressive ART.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mBio.00099-21
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 2557172-2
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  • 5
    Online Resource
    Online Resource
    Dupilumab is very effective in a large cohort of difficult‐to‐treat adult atopic dermatitis patients: First clinical and biomarker results from the BioDay registry
    Wiley ; 2020
    In:  Allergy Vol. 75, No. 1 ( 2020-01), p. 116-126
    Details
    In: Allergy, Wiley, Vol. 75, No. 1 ( 2020-01), p. 116-126
    Abstract: Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab treatment are scarce. Objective To study the effect of 16‐week treatment with dupilumab on clinical response and serum biomarkers in adult patients with moderate‐severe AD in daily practice. Methods Data were extracted from the BioDay registry, a prospective multicenter registry. Sixteen‐week clinical effectiveness of dupilumab was expressed as number of patients achieving EASI‐50 (Eczema Area and Severity Index) or EASI‐75, as well as patient‐reported outcomes measures (Patient‐Oriented Eczema Measure, Dermatology Life Quality Index, Numeric Rating Scale pruritus). Twenty‐one biomarkers were measured in patients treated with dupilumab without concomitant use of oral immunosuppressive drugs at five different time points (baseline, 4, 8, 12, and 16 weeks). Results In total, 138 patients treated with dupilumab in daily practice were included. This cohort consisted of patients with very difficult‐to‐treat AD, including 84 (61%) patients who failed treatment on ≥2 immunosuppressive drugs. At week 16, the mean percent change in EASI score was 73%. The EASI‐50 and EASI‐75 were achieved by 114 (86%) and 82 (62%) patients after 16 weeks of treatment. The most reported side effect was conjunctivitis, occurring in 47 (34%) patients. During dupilumab treatment, disease severity‐related serum biomarkers (TARC, PARC, periostin, and IL‐22), eotaxin‐1, and eotaxin‐3 significantly decreased. Conclusion Treatment with dupilumab significantly improved disease severity and decreased severity‐related serum biomarkers in patients with very difficult‐to‐treat AD in a daily practice setting.
    Type of Medium: Online Resource
    ISSN: 0105-4538 , 1398-9995
    URL: Issue
    URL: Article
    DOI: 10.1111/all.v75.1
    DOI: 10.1111/all.14080
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2003114-2
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  • 6
    Online Resource
    Online Resource
    Control of Human Anelloviruses by Cytosine to Uracil Genome Editing
    American Society for Microbiology ; 2022
    In:  mSphere Vol. 7, No. 6 ( 2022-12-21)
    Details
    In: mSphere, American Society for Microbiology, Vol. 7, No. 6 ( 2022-12-21)
    Abstract: Anelloviruses are the most common viruses infecting humans. Every human carries a nonpathogenic personal anellovirus virome (anellome), yet it is unknown which mechanisms contribute to its stability. Here, we assessed the dynamics and impact of a host antiviral defense mechanism—cytidine deaminase activity leading to C to U editing in anelloviruses—on the stability of the anellome. We investigated anellome sequence data obtained from serum samples collected every 6 months from two healthy subjects followed for more than 30 years. The subjects were infected by a total of 64 anellovirus lineages. Minus-stranded C to U editing was observed in lineages belonging to the Alpha- , Beta- , and Gammatorquevirus genera. The edited genomes were present within virus particles, therefore editing must have occurred at the late stages of the virus life cycle. Editing was favored by 5′-T C contexts in the virus genome, indicating that apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like, catalytic subunit 3 or A3 (APOBEC3) proteins are involved. Within a lineage, mutational dynamics varied over time and few fixations of mutations were detected, indicating that C to U editing is a dead end for a virus genome. We detected an editing coldspot in the GC-rich regions, suggesting that the GC-rich region is crucial for genome packaging, since only packaged virus particles were included in the analysis. Finally, we noticed a lineage-specific reduced concentration after an editing event, yet no clearance. In conclusion, cytidine deaminase activity does not clear anelloviruses, nor does it play a major role in virus evolution, but it does contribute to the stability of the anellome. IMPORTANCE Despite significant attention on anellovirus research, the interaction between the anellovirus virome and the human host remains unknown. We show the dynamics of APOBEC3-mediated cytidine deaminase activity on anelloviruses during a 30-year period of chronic infection and postulate that this antiviral mechanism controls anelloviruses. These results expand our knowledge of anellovirus-host interactions, which may be important for the design of gene therapies.
    Type of Medium: Online Resource
    ISSN: 2379-5042
    URL: Article
    DOI: 10.1128/msphere.00506-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2844248-9
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  • 7
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    Online Resource
    Pediatric acute flaccid myelitis: Evaluation of diagnostic criteria and differentiation from other causes of acute flaccid paralysis
    Elsevier BV ; 2023
    In:  European Journal of Paediatric Neurology Vol. 44 ( 2023-05), p. 28-36
    Details
    In: European Journal of Paediatric Neurology, Elsevier BV, Vol. 44 ( 2023-05), p. 28-36
    Type of Medium: Online Resource
    ISSN: 1090-3798
    URL: Article
    DOI: 10.1016/j.ejpn.2023.03.002
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2009085-7
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  • 8
    Online Resource
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    Early-Life Colonization by Anelloviruses in Infants
    MDPI AG ; 2022
    In:  Viruses Vol. 14, No. 5 ( 2022-04-22), p. 865-
    Details
    In: Viruses, MDPI AG, Vol. 14, No. 5 ( 2022-04-22), p. 865-
    Abstract: Anelloviruses (AVs) are found in the vast majority of the human population and are most probably part of a healthy virome. These viruses infect humans in the early stage of life, however, the characteristics of the first colonizing AVs are still unknown. We screened a collection of 107 blood samples from children between 0.4 and 64.8 months of age for the presence of three AV genera: the Alpha-, Beta- and Gammatorquevirus. The youngest child that was positive for AV was 1.2 months old, and a peak in prevalence (100% of samples positive) was reached between the twelfth and eighteenth months of life. Intriguingly, the beta- and gammatorqueviruses were detected most at the early stage of life (up to 12 months), whereas alphatorqueviruses, the most common AVs in adults, increased in prevalence in children older than 12 months. To determine whether that order of colonization may be related to oral transmission and unequal presence of AV genera in breast milk, we examined 63 breast milk samples. Thirty-two percent of the breast milk samples were positive in a qPCR detecting beta- and gammatorqueviruses, while alphatorqueviruses were detected in 10% of the samples, and this difference was significant (p = 0.00654). In conclusion, we show that beta- and gammatorqueviruses colonize humans in the first months of life and that breastfeeding could play a role in AV transmission.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v14050865
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2516098-9
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  • 9
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    Online Resource
    Diversity and Long-Term Dynamics of Human Blood Anelloviruses
    American Society for Microbiology ; 2022
    In:  Journal of Virology Vol. 96, No. 11 ( 2022-06-08)
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 96, No. 11 ( 2022-06-08)
    Abstract: Anelloviruses (AVs) are commensal members of the human blood virome. Even though it was estimated that over 90% of the human population carries AVs, the dynamics of the AV virome (“anellome”) are unknown. We investigated the dynamics of blood anellomes in two healthy people followed up for more than 30 years. Both subjects were positive for AVs in the majority of samples. Alphatorquevirus (torque teno virus [TTV]) was the most common genus in both subjects, followed by Betatorquevirus (torque teno minivirus [TTMV]) and Gammatorquevirus (torque teno midivirus [TTMDV]). Almost five times more lineages were found in subject 1 than in subject 2, and the anellomes differed phylogenetically. Both anellomes remained compositionally stable, and 9 out of 64 AV lineages were detected in over half of the time points. We confirmed the long-term and short-term persistence of 13 lineages by specific quantitative PCR (qPCR). AV lineages were detected in blood for over 30 years. Noticeable differences in anellome richness were found between the tested subjects, but both anellomes remained compositionally stable over time. These findings demonstrate that the human blood anellome is personal and that AV infection is chronic and potentially commensal. IMPORTANCE Knowledge of the persistence of AVs in humans is crucial to our understanding of the nature of AV infection (chronic or acute) and the role of AV in the host. We therefore investigated the dynamics of anellovirus infection in two healthy people followed up for 30 years. Our findings suggest that the human blood anellovirus virome (anellome) remains stable and personal for decades.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/jvi.00109-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1495529-5
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  • 10
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    Online Resource
    Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART
    American Society for Clinical Investigation ; 2020
    In:  JCI Insight Vol. 5, No. 6 ( 2020-3-26)
    Details
    In: JCI Insight, American Society for Clinical Investigation, Vol. 5, No. 6 ( 2020-3-26)
    Type of Medium: Online Resource
    ISSN: 2379-3708
    URL: Article
    URL: Article
    DOI: 10.1172/jci.insight.134196
    DOI: 10.1172/jci.insight.134196DS1
    Language: English
    Publisher: American Society for Clinical Investigation
    Publication Date: 2020
    detail.hit.zdb_id: 2874757-4
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