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Bruno, R.

Publications and source records attributed to Bruno, R..

5 recordsLinked to original sources

First identification of camel prion disease in Tataouine, Tunisia: an emerging animal prion disease in North Africa

Prion diseases are fatal neurodegenerative disorders affecting humans and animals. Among these, camel prion disease (CPrD) was recently identified in Algeria as a novel disease. In this study, we report six CPrD cases in dromedary camels (Camelus dromedarius) from Tunisia, providing further evidence of its occurrence in North Africa. Affected animals exhibited neurological signs and showed PrPSc accumulation in both brain and lymphoid tissues. Molecular and pathological analyses revealed features consistent with Algerian CPrD cases and distinct from classical scrapie and bovine spongiform encephalopathy. The detection of PrPSc in lymphoid organs, together with the relatively young age of some affected individuals, suggests the possibility of a contagious etiology, including potential vertical or early-life transmission mechanisms, as observed in scrapie and chronic wasting disease affecting small ruminants and cervids, respectively. These findings underscore the need for continued surveillance and further investigation into the epidemiology, transmission mechanisms and potential public health implications of CPrD.

microbiology↗

Navigational Frames of Reference as Critical Regulators of Hippocampal Interneuron Coding Properties

Efficient spatial navigation relies on the hippocampus integrating local (proximal) and global (distal) cues, collectively called frames of reference, to guide behavior and support memory. Although these cues control the anchoring of principal cell fields, how these frames tune interneuron functions remains unknown. Traditionally, interneurons such as O-LM and VIP cells have been viewed primarily as speed encoders, although some also encode spatial information or respond to discrete stimuli. Using calcium imaging in freely behaving mice performing a new spatial learning task that differentiates between reference frames, we demonstrate that O-LM cells displayed a striking bimodal activity pattern, altering both their speed and spatial encoding properties. In contrast, VIP interneurons were largely unaffected by changes in the frame of reference, instead correlating with familiarization. Notably, linear decoding using speed scores revealed that only O-LM interneurons provide an accurate readout of the dominant reference frame, enabling prediction of the animals navigation strategy. These findings highlight that hippocampal interneurons can flexibly adapt their functions depending on cognitive factors such as the reference frames used to guide behavior.

neuroscience↗

Repression of varicella zoster virus gene expression during quiescent infection in the absence of detectable histone deposition

Varicella zoster virus (VZV) is a human-specific herpesvirus that establishes latency in peripheral neurons. The only transcripts detected in infected human trigeminal ganglia (TG) obtained shortly after death correspond to the VZV latency-associated transcript (VLT) and associated VLT-ORF63 splice variants. In vitro studies showed that VLT-ORF63 is translated into a protein (pVLT-ORF63) that induces VZV transcription. The mechanisms that lead to this restricted gene expression and the transition to lytic replication remain unknown, partly due to the difficulty of working with human neurons. In this study, we addressed whether the neuroblastoma-derived cell line SH-SY5Y could serve as a model to investigate the mechanisms that lead to repression of VZV gene expression followed by reactivation. VZV productively infected differentiated SH-SY5Y (dSH-SY5Y) whereas incubation with acyclovir (ACV) inhibited virus replication and induced a progressive repression of the virus. Upon removal of ACV there was production of viral particles in a subset of cells, while others contained non-replicating VZV genomes and VLT-containing transcripts for at least 20 days post-infection (dpi). Exogenous expression of VLT-ORF63 induced productive infection, suggesting that the non-replicating and repressed genomes remained functional. Interestingly, histone deposition was undetectable at VZV genomes in quiescently infected dSH-SY5Y cells, pointing to a potential novel mechanism leading to VZV repression in this neuronal setting.

microbiology↗

Immunity to SARS-CoV-2 up to 15 months after infection

BackgroundInformation concerning the longevity of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in convalescent coronavirus disease-2019 (COVID-19) patients up to 15 months after symptoms onset. MethodsThe levels of anti-spike and anti-receptor binding domain antibodies and neutralizing activities were tested in a total of 188 samples from 136 convalescent patients who experience mild to critical COVID-19. Specific memory B and T cell responses were measured in 76 peripheral blood mononuclear cell samples collected from 54 patients. Twenty-three vaccinated individuals were included for comparison. FindingsFollowing a peak at day 15-28 post-infection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Plasma neutralizing activity against G614 was still detected in 87% of the patients at 6-15 months. Compared to G614, the median neutralizing titers against Beta, Gamma and Delta variants in plasma collected at early (15-103 days) and late (9-15 month) convalescence were 16- and 8-fold lower, respectively. SARS-CoV-2-specific memory B and T cells reached a peak at 3-6 months and persisted in the majority of patients up to 15 months although a significant decrease in specific T cells was observed between 6 and 15 months. ConclusionThe data suggest that antiviral specific immunity especially memory B cells in COVID-19 convalescent patients is long-lasting, but some variants of concern, including the fast-spreading Delta variant, may at least partially escape the neutralizing activity of plasma antibodies. FundingEU-ATAC consortium, the Italian Ministry of Health, the Swedish Research Council, SciLifeLab, and KAW.

immunology↗

Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection

BackgroundThe longevity of the immune response against SARS-CoV-2 is currently debated. We thus profiled the serum anti-SARS-CoV-2 antibody levels and virus specific memory B- and T-cell responses over time in convalescent COVID-19 patients. MethodsA cohort of COVID-19 patients from the Lombardy region in Italy who experienced mild to critical disease and Swedish volunteers with mild symptoms, were tested for the presence of elevated anti-spike and anti-receptor binding domain antibody levels over a period of eight months. In addition, specific memory B- and T-cell responses were tested in selected patient samples. ResultsAnti-SARS-CoV-2 antibodies were present in 85% samples collected within 4 weeks after onset of symptoms in COVID-19 patients. Levels of specific IgM or IgA antibodies declined after 1 month while levels of specific IgG antibodies remained stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG antibodies were still present, though at a significantly lower level, in 80% samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B- and T-cell responses were developed in vast majority of the patients tested, regardless of disease severity, and remained detectable up to 6-8 months after infection. ConclusionsAlthough the serum levels of anti-SARS-CoV-2 IgG antibodies started to decline, virus-specific T and/or memory B cell responses increased with time and maintained during the study period (6-8 months after infection). FundingEuropean Unions Horizon 2020 research and innovation programme (ATAC), the Italian Ministry of Health, CIMED, the Swedish Research Council and the China Scholarship Council.

immunology↗