A brilliant & timely review by Prof. #DianeEGriffin on the persistence of viral RNA following RNA virus infection - which can be associated with late progressive disease or nonspecific lingering symptoms of post-acute infection syndromes (#PAIS). (1/)
First question addressed is WHERE viral RNA can persist. After a variety of RNA virus infection, viral RNA can persist not only in immune privileged sites (brain, eyes, and testes), but also in blood, lymphoid tissue, joints, respiratory tract, GI tissues, and kidney. (2/)
Consequences of persistent viral RNA may include organ-specific as well as nonspecific postviral syndromes such as long COVID, post-Ebola, and post-polio syndromes, characterized by symptoms including fatigue, headache, muscle pain, and joint pain. (3/)
WHAT is the nature of persistent viral RNA? After all, naked viral RNA would be quickly degraded by host RNases. Persistent RNA may be in the form of; 1) Persistent infectious virus 2) Full-length viral RNA 3) Degraded viral RNA
Evidence for 1) and 2) are discussed. (4/)
Protection of viral RNA may be mediated by ribonucleocapsid (for negative-strand viruses) or association with membranous structures (for positive-strand viruses). More studies are needed to understand HOW vRNA persists. (5/)
Viral RNA persistence reflects the ability of infected cells to avoid elimination by immune mechanisms - innate immunity, antibodies and T cells. This explains viral RNA persistence in long-lived cells like neurons. What about persistence in short-lived cells? (6/)
Short-lived cells like epithelial cells commonly permit rapid cell-to-cell transfer of viral nucleocapsids without release of virus from the cell surface that may foster persistence of viral RNA long after infectious virions can be recovered 🤯 (7/)
Persistent viral RNA can drive chronic innate immune stimulation. If viral RNA is translated, the proteins can also drive chronic adaptive immune stimulation that can lead to prolonged inflammation, as discussed by @jan_choutka@mhornig et al. (8/)
Persistence of viral RNA may also be beneficial if it occurs in the lymph nodes. Measles virus infection in NHP led to vRNA persistence, increase in germinal centers B cells and virus-specific TFH and affinity maturation of antiviral antibody. (9/)
Her review ends with these wise words, “Identification of the role of RNA persistence in late disease could be advanced with longitudinal studies that evaluate treatments that suppress RNA replication and examine their effects on RNA persistence and long-term outcomes.” (10/)
Reflection: persistent viral RNA has been seen post-COVID and after other viral infections. Targeting and getting rid of such RNA may hold key to the treatment of #longCOVID and #MECFS patients who suffer from this pathogenesis. (End)
• • •
Missing some Tweet in this thread? You can try to
force a refresh
Published today! Victoria Bastos, @KerrieGreene_ et al found two distinct immunotypes of ME/CFS based on the cerebrospinal fluid analysis. Great collaboration with @MBVanElzakker @microbeminded2 and the Bragée clinic in Sweden. (1/) academic.oup.com/jimmunol/artic…
This is perfect timing as Victoria will present these data at the @polybioRF symposium today. (2/)
Based on cerebrospinal fluid cytokines, we identified two clusters of ME/CFS patients. Cluster 1 had elevated matrix metalloproteinases & many cytokines compared to cluster 2. Other than older age (Cluster 1), clinical presentation of these clusters was similar. (3/)
Published today📣
Our nasal booster in the "Prime & Spike" vaccine works without adjuvants (which are needed to induce adaptive immunity but also cause inflammation). @Kwon_Dongil @tianyangmao @BenIsraelow et al. asked how this is possible. (1/) nature.com/articles/s4159…
Prime & Spike is a vaccine strategy that leverages preexisting immunity primed by conventional vaccines to elicit mucosal IgA and T cell responses that prevent COVID infection and transmission in rodents. The nasal booster is simply the spike protein (2/) science.org/doi/10.1126/sc…
Our new study shows that the nasal spike protein booster converts lymph node memory B cells into IgA-secreting cells in the lung with the help of memory CD4 T cells. Ag-specific CD4 T cells replace all the necessary functions of adjuvants without nonspecific inflammation! (3/)
This prospective observational study led by @connorbgrady @bornali_27 @SilvaJ_C @hmkyale examined the impact of the primary COVID-19 vaccination on the symptoms and immune signatures of 16 people with #longCOVID. Here is what we found 👇🏼 (1/)
This study asked: Does COVID vaccination improve symptoms of long COVID? If so, is the improvement due to robust T and B cell responses leading to the clearance of the viral reservoir? If not, is there an immune feature that predicts worsening of LC? (2/)
The self-reported impact of vaccination was variable. Of the 16 long COVID patients, 10 felt better, 3 had no change, and 3 had worse health (1 hospitalized) 12 weeks after vaccination. Both physical and social effects of symptom burden appeared to decrease after vaccination. (3/)
Our preprint on post-vaccination syndrome is out. We studied immune signatures and examined spike protein in the blood of people who have developed chronic illnesses after COVID-19 vaccination. (1/) medrxiv.org/content/10.110…
Vaccines have saved countless lives and inspired me to become an immunologist. While generally safe, some people experience adverse effects, including Post-Vaccination Syndrome (PVS). Studying PVS is crucial for improving patient care and enhancing vaccine safety & acceptance. (2/) pubmed.ncbi.nlm.nih.gov/37986769/
Happy to share our latest work by @YYexin et al. on antibody-mediated control of endogenous retroviruses in mice. In the process, we found “natural antibodies” with broad reactivity against enveloped viruses. Here is how “panviral” antibodies work 🧵(1/)
Endogenous retroviruses (ERV) are remnants of genetic invaders that have integrated into our ancestors' genomes over millions of years. ERVs occupy ~8% of the human genome and are under constant host immune surveillance. (2/) nature.com/articles/nrg31… nature.com/articles/nrmic…
This work started over 7 years ago when @YYexin and @rebecca_treger began to examine why ERVs reactivate in certain mouse strains. Through many genetic crosses, we figured out that secreted IgM recruits complement to suppress infectious ERV from emerging. (3/)
This time, we developed a nasal booster vaccine for influenza viruses. In this preprint, @MiyuMoriyama et al. show that nasal boosters with unadjuvanted hemagglutinin protein induce sterilizing immunity in mice against flu. (1/) biorxiv.org/content/10.110…
This work builds on the Prime and Spike vaccine strategy by @tianyangmao @BenIsraelow et al. against COVID where mRNA vaccine followed by nasal booster with recombinant spike protein established local immunity, ⬇️ infection & transmission in rodents. (2/) science.org/doi/10.1126/sc…
For Prime and HA against flu, @MiyuMoriyama tested several different mRNA IM prime and nasal HA booster doses, followed by a homologous influenza virus challenge. Like Prime and Spike, no adjuvant is needed for the nasal booster due to preexisting immunity from Prime. (3/)