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Amy Proal, PhD Profile picture
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Jul 14 • 4 tweets • 2 min read
New @polybioRF podcast 👉 I interviewed Dr. Diane Griffin: A Chair of Molecular Microbiology/Immunology at Johns Hopkins. We discuss RNA virus persistence w/ implications for LongCovid. Listen on Spotify (open.spotify.com/episode/4ICxWL…) or watch on Youtube ()
2/ Diane explains how RNA from viruses such as measles, Ebola, Zika and SARS-CoV-2 can perisist in host cells for years after acute infection despite patients not being overtly infectious. This viral RNA is often transcriptionally active and can modulate the host immune response
3/ In fact these RNA #viruses have evolved many mechanisms to maintain RNA persistence in host cells. These include extending the lives of infected cells, or trimming parts of their genomes to better evade immune detection (paper below by Dr. Griffin): journals.plos.org/plosbiology/ar…
4/ Diane discusses how studying long-term #SARS-CoV-2 RNA and antigen persistence in a wide range of body sites (viral reservoir) should be a central #LongCovid research topic

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More from @microbeminded2

Amy Proal, PhD Profile picture
Jun 11
This important study found a significantly elevated frequency of #SARS-CoV-2-specific TNF-α-producing CD8+ T cells in patients with pulmonary #LongCovid (PASC). PASC subjects experienced an average symptom duration of over 6 months: journals.plos.org/plospathogens/…
2/ This is how the authors interpret the finding: "This increased frequency could be detected in response to peptide pools of all the #viral structural proteins in comparison to the resolved #COVID-19 (RC) cohort.
3/ Interestingly, these T cells were also significantly higher in female PASC participants compared to males, which may contribute to the higher prevalence of PASC in #women
Read 10 tweets
Amy Proal, PhD Profile picture
Feb 21
This is the most straightforward explanation for chronic symptoms in at least a subset of #LongCovid patients. Partly b/c if the #virus is still present its activity can directly contribute to other phenomena also being documented in LongCovid
2/ Persistence of #SARS-CoV-2 in tissue could lead to shedding of spike protein into blood, which can catalyze the ongoing formation of microclots and hyperactivated platelets
3/ Persistence of SARS-CoV-2 can lead to ongoing downregulation of interferon and/or T cell signaling by the virus, creating an optimal atmosphere for activation of EBV or other #pathogens normally controlled by such immunity
Read 10 tweets
Amy Proal, PhD Profile picture
Feb 10
New @polybioRF podcast. I interviewed Dr. Tobias Lanz: MD + researcher in the lab of Prof. William Robinson at the Department of Rheumatology/Immunology at Stanford School of Medicine. Listen on Spotify (open.spotify.com/episode/4bTQss…) or watch on Youtube ()
2/ In the interview Tobias discusses this breakthrough study he led at Stanford. It showed that a cross-reactive antibody can contribute to #MS neuroinflammation thanks to molecular mimcry b/t an EBV viral protein (EBNA1) + a human CNS protein (GlialCAM): nature.com/articles/s4158…
3/ Tobias also describes this recent Harvard study which further implicates #EBV as a driver of MS. He talks about treatment for MS now that #viral activity is understood to be at the heart of the disease process: science.org/doi/10.1126/sc…
Read 7 tweets
Amy Proal, PhD Profile picture
Jan 8
New @polybioRF podcast: I interviewed Dr. Alessio Fasano: Chief of the Division of Pediatric Gastroenterology & Nutrition at MassGeneral Hospital for Children. Watch on Youtube () or listen on an App like Spotify (open.spotify.com/episode/3KZGCX…)
2/ Alessio discusses this study: His team showed that in children with MIS-C, #SARS-CoV-2 gut reservoir led to release of zonulin (a biomaker of intestinal permeability) + subsequent trafficking of spike protein to into blood, leading to hyperinflammation: pubmed.ncbi.nlm.nih.gov/34032635/ Image
3/ Alessio and team are using a zonulin inhibitor called Larazotide to improve gut permeability/SARS-CoV-2 spike leakage in #MIS-C (the drug may also have antviral properties). They are ready to start a Larazotide trial in #LongCovid too if funded
Read 4 tweets
Amy Proal, PhD Profile picture
Dec 28, 2021
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish Hey! Well hypoxic tissue cld lead to lower O2 extraction, & infected tissue is often hypoxic. Most intracellular pathogens hijack metabolism of cells they infect & “push” host mitochondrial metabolism to anerobic glycolysis (O2 not being used for OXPHOS): ij.hapres.com/htmls/IJ_1341_…
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 2/ In fact many intracellular #pathogens either directly or indirectly enhance hypoxia inducible factor (HIF-1) stability. HIF-1 is a key glycolytic regulator/transcription factor whose stability reduces reliance on OXPHOS by initiating glycolytic #metabolism
@kimisgubbed @VirusesImmunity @KaminskiMed @Be_Kinderr @jenbrea @ahandvanish 3/ With that in mind @VirusesImmunity, it was interesting that in your brain organoid model, you showed SARS-CoV-2 capable of infecting neurons, where it induced a locally hypoxic environment as measured by staining for HIF-1 alpha: pubmed.ncbi.nlm.nih.gov/33433624/
Read 11 tweets
Amy Proal, PhD Profile picture
Dec 23, 2021
People are asking me: what if we did a similar autopsy study to look for #viruses in ME/CFS? Well, several teams that performed single autopsy studies on #ME/CFS patients found evidence of persistent enterovirus infection in subject brain/body tissue
2/ Enteroviruses are (like SARS-CoV-2) single-stranded RNA viruses. They include the coxsackieviruses, poliovirus, echoviruses + rhinoviruses. These viruses cause about 10–15 million #infections each year in the USA alone
3/ This 1994 ME/CFS autopsy study identified positive PCR sequences with similarity to coxsackievirus B3 in samples from the #brainstem and hypothalamus (and also in muscle and heart tissue): acpjournals.org/doi/10.7326/00…
Read 7 tweets

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