Biology subjects

de Vries, L.

Publications and source records attributed to de Vries, L..

5 recordsLinked to original sources

bioRxiv2026

Larger inducible reservoir and higher abundance of exhausted CD8+ T cells in people treated after late versus non-late diagnosis of chronic HIV one year after ART initiation

Background Despite effective antiretroviral therapy, HIV-1 remains a global health challenge. Most people living with HIV (PWH) are diagnosed in the chronic stage and around half are diagnosed late globally. Insight into the effect of time of diagnosis and therapy initiation on reservoir dynamics and immune reconstitution within the group with a chronic diagnosis is limited. Methods In this prospective cohort study, PWH diagnosed during the chronic stage (from Fiebig VI) were stratified into late (<350 CD4+ T cells/mm3 or an AIDS-defining illness) or non- late diagnosis subgroups. We analyzed the viral reservoir by IPDA, SQuHIVLa and FISH-Flow, and the immune compartment with the HIV-specific AIM assay and a 45-color spectral flow cytometry panel in the first year after ART initiation. Findings Although proviral DNA decreased during the first year of ART, the inducible reservoir remained stable. One year after ART initiation, exhausted CD8+ T cell abundance correlated significantly with CD4+ T cell count pre-ART. PWH with a late diagnosis had a significantly higher inducible reservoir and lower CD4+ T-cell counts than the non-late HIV diagnosis subgroup. Moreover, the subgroup with a late diagnosis showed higher abundance of exhausted CD8+ T cells, higher expression of activation/exhaustion markers, and lower naive CD4+ T-cell abundance than the non-late diagnosis subgroup. Interpretation Our results show that late diagnosis is associated with a persistently higher inducible viral reservoir and impaired immune recovery. These findings underline the importance of early diagnosis and treatment, and rationalize the use of late diagnosis as a covariate in future cure and reservoir studies.

immunology↗

bioRxiv2022

A country-wide examination of effects of urbanization on common birds

Urbanization forms one of the most drastic alterations of the environment and poses a major threat to wildlife. The human-induced modifications of the landscape may affect individuals fitness and thereby result in population declines. Research on how urbanization affects fitness traits has shown mixed results, but typically contrasted data from few urban and non-urban sites collected over short time frames from single species. It thus remains unknown whether we can generalize across species, whereas such knowledge is crucial for population predictions that are needed for conservation management. Here, we use data from a nation-wide citizen science project to examine variation in survival and body mass and size of common passerine birds, collected along an urbanization gradient in the Netherlands over an 8-year period. Although the overall association between urbanization and survival was slightly negative, there was strong support for lower survival in three species, and higher survival in two of the 11 species examined. Effects of urbanization on body mass and size also varied but were far less strong and there was no evidence that they mediated the impacts on survival. Our results imply that body mass and size cannot be used as indicators for urban-associated patterns of survival. Furthermore, the species-specific survival responses indicate that care should be taken when predicting the effects of ongoing urbanization for communities, because even closely related species can show different responses. Moreover, the contrasting survival successes among species suggests that ongoing urbanization may lead to shifts in community structure and loss of biodiversity.

ecology↗

bioRxiv2022

The SARS-CoV-2 accessory factor ORF7a downregulates MHC class I surface expression

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 500 million infections and more than six million deaths worldwide. Although the viral genomes of SARS-CoV-1 and SARS-CoV-2 share high sequence homology, the clinical and pathological features of COVID-19 differ profoundly from those of SARS. It is apparent that changes in viral genes contribute to the increased transmissibility of SARS-CoV-2 and pathology of COVID-19. Cytotoxic T lymphocytes play a key role in the elimination of virus-infected cells, mediated by recognition of virus-derived peptides that are presented on MHC class I molecules. Here, we show that SARS-CoV-2 can interfere with antigen presentation thereby evading immune surveillance. SARS-CoV-2 infection of monkey and human cell lines resulted in reduced cell-surface expression of MHC class I molecules. We identified a single viral gene product, the accessory factor open reading frame 7a (ORF7a), that mediates this effect. ORF7a interacts with HLA class I molecules in the ER, resulting in ER retention or impaired HLA heavy chain (HC) trafficking to the Golgi. Ultimately, these actions result in reduced HLA class I surface expression on infected cells. Whereas ORF7a from SARS-CoV-2 reduces surface HLA class I levels, the homologous ORF7a from the 2002 pandemic SARS-CoV-1 did not, suggesting that SARS-CoV-2 ORF7a acquired the ability to downregulate HLA-I during evolution of the virus. We identified a single amino acid in the SARS-CoV-1 ORF7a luminal domain that, upon mutating to the corresponding SARS-CoV-2 ORF7a sequence, induced a gain-of-function in HLA surface downregulation. By abrogating HLA class I antigen presentation via ORF7a, SARS-CoV-2 may evade host immune responses by inhibiting anti-viral cytotoxic T cell activity, thereby contributing to the pathology of COVID-19.

microbiology↗

bioRxiv2019

Human cytomegalovirus nuclear capsid motility is non-directed and independent of nuclear actin bundles

Herpesvirus genome replication, capsid assembly and packaging take place in the host cell nucleus. Matured capsids leave the nucleus through a unique envelopment-de-envelopment process at the nuclear membranes called nuclear egress. How assembled and DNA-containing herpesvirus capsids reach the sites of nuclear egress is however still controversially discussed, as host chromatin that marginalizes during infection might constitute a major barrier. For alphaherpesviruses, previous work has suggested that nuclear capsids use active transport mediated by nuclear filamentous actin (F-actin). However, direct evidence for nuclear capsid motility on nuclear F-actin was missing. Our subsequent work did not detect nuclear F-actin associated with motile capsids, but instead found evidence for chromatin remodeling to facilitate passive capsid diffusion. A recent report described that human cyto-megalovirus, a betaherpesvirus, induces nuclear F-actin and that the motor protein myosin V localizes to these structures. Direct evidence of capsid recruitment to these structures and motility on them was however missing. In this study, we tested the functional role of HCMV-induced, nuclear actin assemblies for capsid transport. We did not observe transport events along nuclear F-actin. Instead, reproduction of nuclear F-actin was only possible using strong overexpression of the fluorescent marker LifeAct-mCherry-NLS. Also, two alternative fluo-rescent F-actin markers did not detect F-actin in HCMV-infected cells. Furthermore, single particle tracking of nuclear HCMV capsids showed no indication for active transport, which is in line with previous work on alphaherpesviruses.

microbiology↗

bioRxiv2019

Mouse vendor influence on the bacterial and viral gut composition exceeds the effect of diet

Often physiological studiess using mice from one vendor show different outcome when being reproduced using mice from another vendor. These divergent phenotypes between similar mouse strains from different vendors have been assigned to differences in the gut microbiome. During recent years, evidence has mounted that the gut viral community plays a key role in shaping the gut microbiome and may thus also influence mouse phenotype. However, to date inter-vendor variation in the murine gut virome has not been studied. Using a metavirome approach, combined with 16S rRNA gene sequencing, we here compare the composition of the viral and bacterial gut community of C57BL/6N mice from three different vendors exposed to either a chow-based low-fat diet or high-fat diet. Interestingly, both the bacterial and the viral component of the gut community differed significantly between vendors. The different diets also strongly influenced both the viral and bacterial gut community, but surprisingly the effect of vendor exceeded the effect of diet. In conclusion, the vendor effect is substantial on not only the gut bacterial community, but also strongly influences viral community composition. Given the effect of GM on mice phenotype this is essential to consider, for increasing reproducibility of mouse studies.

microbiology↗