Biology subjects

Manuelidis, L.

Publications and source records attributed to Manuelidis, L..

3 recordsLinked to original sources

bioRxiv2020

Detection of long SARS-CoV-2 nucleocapsid sequences in peripheral blood monocytes collected soon after hospital admission

Many viruses infect circulating mononuclear cells thereby facilitating infection of diverse organs. Blood monocytes (PBMC) are being intensively studied as immunologic and pathologic responders to the new SARS-CoV-2 virus (CoV19) but direct evidence showing CoV19 in monocytes is lacking. Circulating myeloid cells that take up residence in various organs can harbor viral genomes for many years in lymphatic tissues and brain, and act as a source for re-infection and/or post-viral organ pathology. Because nucleocapsid (NC) proteins protect the viral genome we tested PBMC from acutely ill patients for the diagnostic 72bp NC RNA plus adjacent longer (301bp) transcripts. In 2/11 patient PBMC, but no uninfected controls, long NCs were positive as early as 2-6 days after hospital admission as validated by sequencing. Pathogenic viral fragments, or the infectious virus, are probably disseminated by rare myeloid migratory cells that incorporate CoV19 by several pathways. Predictably, these cells carried CoV19 to heart and brain educing the late post-viral pathologies now evident.

microbiology↗

bioRxiv2019

Prokaryotic SPHINX sequences are conserved in mammalian brain and participate in neurodegeneration

A new class of circular mammalian \"SPHINX\" DNAs, represented by the 1.8 and 2.4kb elements, were discovered in highly infectious cytoplasmic particles isolated from Creutzfeldt-Jakob Disease (CJD) and scrapie samples. These DNAs contained replication initiation sequences (REPs) with [~]70% homology to Acinetobacter phage REP segments. Antibodies against REP peptides from the 1.8kb DNA highlighted a 41kDa protein (spx) on Western blots, and in-situ studies revealed its tissue and cell-type specific expression, e.g., in pancreatic islet cells, keratinocytes and kidney tubules but not pancreatic exocrine cells, alveoli, and striated muscle. An intense spx signal in oocytes implicated maternal inheritance of the SPHINX 1.8 genome, a feature known only for bacterially derived mitochondrial DNA in mammals. To determine if spx concentrated at specific neurons and synapses, and also maintained a conserved pattern of architectural organization in mammals, we evaluated mouse, rat, hamster, Guinea Pig and human brains. Most outstanding was the cross-species concentration of spx in huge excitatory synapses of mossy fibers and small internal granule neuron synapses, the only excitatory neuron within the cerebellum. This synaptic localization was also demonstrable at the ultrastructural level. Vacuolar loss of these synaptic complexes, thinning of the internal granule cell layer, and pathological fibrillar spx accumulations within Purkinje neurons were obvious in CJD Guinea pig brains. In rats, these fibrillar changes marked hippocampal Pyramidal neurons and preceded prion protein misfolding. Spx may define different causes or processes of neurodegeneration. The evolutionary origin, persistence and modulation of SPHINX 1.8 opens an unexpected chapter in mammalian symbiosis.

evolutionary biology↗

bioRxiv2018

The prokaryotic SPHINX 1.8 REP protein is tissue-specific and expressed in human germline cells

Small circular DNAs of 1.8 and 2.4kb were initially discovered in highly infectious CJD and scrapie particles from mammalian brain and cultured cells. Surprisingly, these protected cytoplasmic \"SPHINX\" DNAs contained replication (REP) initiation sequences resembling those of Acinetobacter phage viruses. An antibody was generated against a REP peptide encoded by the SPHINX 1.8 ORF that was not present in mammals. It bound to a 41kd \"spx1\" protein on Western blots. Cytologically, spx1 concentrated in spinal cord synapses and pancreatic islet, but not exocrine cells. We hypothesized that circular SPHINX DNAs are ancient symbiotic elements that can participate in functional differentiation and neurodegeneration. Cell and tissue specific patterns of spx1 expression shown below implicate somatic cell-to-cell communication and differentiation functions that would favor conservation of SPHINX 1.8 in evolution. Remarkably, primary human oocytes and spermatogonia, but not mature sperm, displayed intense cytoplasmic spx1 signals that underscore the maternal inheritance of SPHINX 1.8. These findings should encourage investigations of unexplored networks of incorporated environmental infectious agents that can be key actors in progressive neurodegeneration, immunity and cancer.

cell biology↗