Biology subjects

Rozenberg, F.

Publications and source records attributed to Rozenberg, F..

3 recordsLinked to original sources

bioRxiv2026

Experimental and natural peripheral HSV-1 infection: Neurotropism and impact on Alzheimer's disease-related molecular markers

Herpes Simplex virus type 1 (HSV-1) is a highly prevalent neurotropic virus from the alphaherpesviruses family. In recent years, a growing body of research has focused on the potential role of HSV-1 infections and recurrent reactivations in the pathophysiology of Alzheimers disease (AD). In particular, it has been hypothesized that HSV-1 could initiate or amplify the formation of neuropathological lesions characteristic of AD. To explore further this hypothesis, we adopted an integrated approach aiming at deciphering the impact of HSV-1 infection on AD molecular markers (A{beta} and Tau pathologies) and combining experimental animal models of in vivo infection, postmortem neuropathological analysis of AD brains, as well as in-vivo clinical analysis in AD patients. In animal models of peripheral (labial) infection with HSV-1 virus, we analyzed viral dissemination from peripheral tissues to the CNS, and the associated neuropathological consequences. Histological and molecular analyses revealed the occurrence of viral material (RNA, proteins) in the brainstem, the primary site of viral neuroinvasion, and in more anterior regions of the brain. Viral signatures were accompanied by early abnormal deposits of A{beta} peptides and accumulation of phosphoTau (pTau) proteins in various brain areas. Neuropathological examination of AD/control participants also underlined the presence of HSV-1 DNA in the human brainstem (pons) that was always associated with local A{beta}/Tau aggregates. Finally, in AD patients, associations were found between HSV-1 seropositivity and neuropathological lesion burden (region-specific Tau and A{beta} deposition detected by neuroimaging). Taken together, these data provide new evidence in favor of the involvement of HSV-1 in the pathophysiology of AD, stressing a possible causal link between HSV-1 infection, neuroinvasion and AD neuropathological hallmarks (A{beta} lesions and tauopathy).

neuroscience↗

bioRxiv2021

Differential levels of IFNα subtypes in autoimmunity and viral infection

Type I interferons are essential for host response to viral infections, while dysregulation of their response can result in autoinflammation or autoimmunity. Among IFN (alpha) responses, 13 subtypes exist that signal through the same receptor, but have been reported to have different effector functions. However, the lack of available tools for discriminating these closely related subtypes, in particular at the protein level, has restricted the study of their differential roles in disease. We developed a digital ELISA with specificity and high sensitivity for the IFN2 subtype. Application of this assay, in parallel with our previously described pan-IFN assay, allowed us to study different IFN protein responses following cellular stimulation and in diverse patient cohorts. We observed different ratios of IFN protein responses between viral infection and autoimmune patients. This analysis also revealed a small percentage of autoimmune patients with high IFN2 protein measurements but low pan-IFN measurements. Correlation with an ISG score and functional activity showed that in this small sub group of patients, IFN2 protein measurements did not reflect its biological activity. This unusual phenotype was partly explained by the presence of anti-IFN auto-antibodies in a subset of autoimmune patients. This study reports ultrasensitive assays for the study of IFN proteins in patient samples and highlights the insights that can be obtained from the use of multiple phenotypic readouts in translational and clinical studies.

immunology↗

bioRxiv2020

Human T-bet governs innate and innate-like adaptive IFN-γ immunity against mycobacteria

Inborn errors of human IFN-{gamma} immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to an inherited deficiency of the transcription factor T-bet. This deficiency abolishes the expression of T-bet target genes, including IFNG, by altering chromatin accessibility and DNA methylation in CD4+ T cells. The patient has profoundly diminished counts of mycobacterial-reactive circulating NK, invariant NKT (iNKT), mucosal-associated invariant T (MAIT), and V{delta}2+ {gamma}{delta} T lymphocytes, and of non-mycobacterial-reactive classic TH1 lymphocytes, the remainders of which also produce abnormally low amounts of IFN-{gamma}. Other IFN-{gamma}-producing lymphocyte subsets however develop normally, but with low levels of IFN-{gamma} production, with exception of V{delta}2- {gamma}{delta} T lymphocytes, which produce normal amounts of IFN-{gamma} in response to non-mycobacterial stimulation, and non-classic TH1 (TH1*) lymphocytes, which produce IFN-{gamma} normally in response to mycobacterial antigens. Human T-bet deficiency thus underlies mycobacterial disease by preventing the development of, and IFN-{gamma} production by, innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and V{delta}2+ {gamma}{delta} T cells), with mycobacterial-specific, IFN-{gamma}-producing, purely adaptive {beta} TH1* cells unable to compensate for this deficit.

immunology↗