Biology subjects

Kraus, T. V.

Publications and source records attributed to Kraus, T. V..

2 recordsLinked to original sources

bioRxiv2026

HIV-1 promotes cell-to-cell interactions enabling spread from CD4+ T cells to microglia

HIV-1 infection of the brain occurs early in acute infection and results in neuroinflammation and - when untreated - in cognitive impairment, yet the mechanisms by which microglia become infected remain poorly defined. Evidence from simian immunodeficiency virus (SIV) studies supports a model in which infected CD4+ T cells disseminate HIV-1 to tissue macrophages, but this has not yet been confirmed for human microglia. Here, we used human monocyte-derived microglia (MDMi) and autologous HIV-1-infected primary CD4+ T cells to investigate viral transmission and immune cell interactions. Transcriptional profiling of MDMi confirmed microglia signature genes such as CX3CR1, P2RY12 and C1QB, and surface staining showed expression of CD4 and the HIV-1 coreceptor CCR5. Compared to cell-free infection, direct cell-to-cell contact between MDMi and HIV-1-infected CD4+ T cells markedly enhanced productive infection of MDMi. HIV-1 infection downmodulated the "dont-eat-me" signal CD47 and increased phosphatidylserine on the surface of primary CD4+ T cells. Consequently, HIV-1 infection of primary CD4+ T cells increased microglia-CD4+ T cell interactions and resulted in enhanced phagocytosis by MDMi. Together, this supports a mechanism where HIV-1 facilitates cell-to-cell spread from primary CD4+ T cells to microglia, which has important implications for therapeutic targeting of HIV-1 brain reservoir seeding.

immunology↗

bioRxiv2025

Proteome-wide impact of LRRK1 and 2 inhibitors on protein interactions and phosphorylation

The Leucine-rich repeat kinases 1 and 2 (LRRK1 and 2) are large, multidomain proteins and closely related members of the Roco protein family. They share a high similarity in domain structure and are both phosphorylate members of the Rab GTPase family. However, despite these similarities, there are substantial differences between the two kinases. While mutations to LRRK1 are only implicated in rare cases of osteopetrosis, LRRK2 is associated with multiple diseases, most prominently with familial and sporadic forms of Parkinsons disease, where pathogenic LRRK2 is associated with an increased kinase activity. While LRRK2 has received major attention from the research community, LRRK1 has been largely understudied. In this work, we employ proximity labelling mass spectrometry in combination with quantitative phosphoproteomics in a model cell line to obtain the cellular interactomes of LRRK1 and LRRK2 and corresponding phosphorylation sites. We then use this dataset to characterize the impact of small molecules targeting both LRRK1 and 2. We identify phosphorylation sites across the proteome that are impacted by these inhibitors and identify novel candidate substrates for LRRK2, including MICALL2. Taken together our data provide a powerful resource for future studies on the cellular role and function of LRRK proteins and their potential use as therapeutic targets.

molecular biology↗