Tomaszewski, M. | bioRxiv Science

bioRxiv2021

Variation in Human Herpesvirus 6B telomeric integration, excision and transmission between tissues and individuals

Human herpesviruses 6A and 6B (HHV-6A/6B) are ubiquitous pathogens that persist lifelong in latent form and can cause severe conditions upon reactivation. They are spread by community-acquired infection of free virus (acqHHV6A/6B) and by germline transmission of inherited chromosomally- integrated HHV-6A/6B (iciHHV-6A/6B) in telomeres. We exploited a hypervariable region of the HHV- 6B genome to investigate the relationship between acquired and inherited virus and revealed predominantly maternal transmission of acqHHV-6B in families. Remarkably, we demonstrate that some copies of acqHHV-6B in saliva from healthy adults gained a telomere, indicative of integration and latency, and that the frequency of viral genome excision from telomeres in iciHHV-6B carriers is surprisingly high and varies between tissues. In addition, newly formed short telomeres generated by partial viral genome release are frequently lengthened, particularly in telomerase-expressing pluripotent cells. Consequently, iciHHV-6B carriers are mosaic for different iciHHV-6B structures, including circular extra-chromosomal forms that have the potential to reactivate. Finally, we show transmission of an HHV-6B strain from an iciHHV-6B mother to her non-iciHHV-6B son. Altogether we demonstrate that iciHHV-6B can readily transition between telomere-integrated and free virus forms.

genetics↗

bioRxiv2019

Co-Registration of Optoacoustic Tomography and Magnetic Resonance Imaging Data from Murine Tumour Models

As optoacoustic tomography emerges as a mainstream preclinical imaging modality, understanding the relationship between optoacoustic and other imaging biomarkers in the context of the underlying tissue biology becomes vitally important. For example, assessment of blood haemoglobin concentration and oxygenation can be achieved using OT, and also by several magnetic resonance imaging (MRI)-based techniques. To evaluate the relationship between these metrics and the relative performance of the two modalities in assessment of haemoglobin physiology, co-registration of their output imaging data is required. Unfortunately, this poses a significant challenge due to differences in the data acquisition geometries. Here, we present an integrated framework for registration of OT and MR image data in small animals. Our framework combines a novel MR animal holder, to improve animal positioning for deformable tissues, and a landmark-based software co-registration algorithm. We demonstrate that our protocol significantly improves registration of both body and tumour contours between these modalities.

bioengineering↗