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Amy Proal, PhD Profile picture
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7 Jun, 4 tweets, 3 min read
If you’re considering studying blockage of GPCRs in #LongCovid or related conditions, please start w/ the understanding that humans are not sterile...and that common human organisms/pathogens express proteins/metabolites that block/dysregulate GPCR signaling
2/ Herpesvirus re-activation is common in #COVID-19, and may impact some LongCovid cases. The herpesviruses alone (EBV, CMV etc) create a wide range of proteins that block GPCR signaling: ncbi.nlm.nih.gov/pmc/articles/P… Indeed, viral hijacking of GPCRs is a big topic in cancer research
3/ Beyond that, many commensal #bacteria derived from the human #microbiome appear capable of expressing metabolites that are GPCR mimics, that directly impact GPCR signaling. That means even changing microbiome dynamics could impact GPCR-related issues: ncbi.nlm.nih.gov/pmc/articles/P…
4/ Indeed, molecular mimicry (sequence homology) between #viral + bacterial GCPR protein/metabolite “mimics” and human CPCR proteins/ligands may account for the generation of “autoantibodies” connected to GPCR signaling issues

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Amy Proal, PhD Profile picture
7 Jun
Preprint reports elevated serum inflammatory cytokine profile in #LongCovid subjects. Worth noting that an ongoing immune response towards persistent viral reservoirs of #SARS-CoV-2 and/or antigen could explain the findings: medrxiv.org/content/10.110…
2/ So the findings underscore the need to do studies that obtain tissue (via surgery or biopsy if possible) to search for #SARS-CoV-2/antigen in #LongCovid patients. Similar to what this team did (and found viral RNA/antigen in multiple tissue types!): gut.bmj.com/content/early/…
3/ Studying both the LongCovid immune response AND possible #viral reservoirs is very important for LongCovid patients to get the best treatment. If you assume the #immune response alone is the problem, standard of care could become immunosuppressive drugs
Read 4 tweets
Amy Proal, PhD Profile picture
1 Jan
Happy 2021! @MBVanElzakker and I are excited to share our new article published in #Immunometabolism: “Pathogens Hijack Host Cell Metabolism: Intracellular Infection as a Driver of the Warburg Effect in Cancer and Other Chronic Inflammatory Conditions”: ij.hapres.com/htmls/IJ_1341_…
2/ In the paper, we detail molecular mechanisms by which #viral, #bacterial, and #parasite intracellular pathogens can induce, or contribute to, a Warburg-like #metabolism in infected host cells in order to meet their own replication and nutritional needs.
3/ We also discuss how host defense towards #infection may impact cellular metabolic changes (including how #mitochondria can participate in the innate immune response towards infection)
Read 9 tweets
Amy Proal, PhD Profile picture
20 Dec 20
It was inspiring to virtually attend the first Inaugural Robert D. Moir Symposium this past Friday. Rob was a friend and constant source of inspiration, plus an amazing sounding board for novel ideas. He passed away from glioblastoma one year ago today.
2/ Like most great scientists I’ve known, Rob was not content to study just the presence or absence of compounds/organisms in the human body. Instead his thinking continually gravitated towards the vital question of “what are they DOING??”
3/ Via that lens - the constant question of “why?” and a passion for characterizing the molecular biology of the “why?”...Rob uncovered that amyloid in the #Alzhiemer’s brain has a function (it appears to act as an antimicrobial peptide)
Read 5 tweets
Amy Proal, PhD Profile picture
12 Dec 20
1/ This excellent study by @aaronmring/@VirusesImmunity and team found that COVID-19 patients exhibit dramatic increases in the production of antibodies against thousands of human extracellular and secreted proteins (the exoproteome) compared to controls 👇
2/ The million dollar question is: what molecular mechanisms underly this antibody/#autoantibody production? It is worth interpreting the findings via the lens of human #microbiome/#virome activity + the activity of persistent pathogens (such as EBV) harbored by study subjects.
3/ Every study subject harbored extensive microbiome/virome communities comprised of trillions of organisms during #COVID-19 infection…with such ecosystems now understood to persist beyond just the gut but also in other body sites (#lung, liver etc).
Read 15 tweets
Amy Proal, PhD Profile picture
10 Dec 20
Important paper 👉 A team in Tokyo took RNA-seq data from the Genomic-#Tissue Expression Project: a public resource created to study tissue-specific gene expression/regulation from 54 tissue types collected from 1000+ healthy individuals at autopsy: bmcbiol.biomedcentral.com/articles/10.11…
2/ They successfully identified 39 viral species in at least one tissue (tissue types included #brain, pituitary, esophagus, thyroid, #heart, breast, lung, kidney, adrenal gland, prostate, #nerve, adipose tissue, blood vessel, ovary, uterus etc)
3/ Viruses identified in the various tissue samples included EBV, HSV-1, Varicella, CMV, HHV6-A/B, HHV-7, HCV, HPV, adeno-associated virus...and 16 RNA #viruses including Respiratory syncytial virus (RSV), Parainfluenza Virus 3..
Read 12 tweets
Amy Proal, PhD Profile picture
23 Nov 20
This is an incredibly important preprint to inform #LongCovid. Among many analyses, the team recruited 4 patients w/ prolonged + recurrent olfactory function loss after #COVID-19 (time from first COVID-19 symptoms to inclusion ranged from 110-196 days): biorxiv.org/content/10.110… Image
2/ None of these patients had detectable COVID-19 #RNA in nasopharyngeal samples by routine diagnosis (RT-qPCR). However, ALL patients had detectable COVID-19 RNA in samples obtained from their olfactory mucosa (confirmed with aRT-qPCR SYBR technique)
3/ Three of the patients had a high COVID-19 #viral load in the olfactory mucosa. Immunostaining additionally revealed the presence of COVID-19 antigens in 3 out of 4 patients. Based on that and related findings the team concluded...
Read 8 tweets

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