Don't you just LOVE when a paper comes out providing an explanation for a long term lab question 😀🎉 Mystery solved!!
This really nice paper just out in #PLOSpathogens
by @FirpoMason and @bryancmounce based at the Loyola University Chicago @LoyolaInDIRI. (a🧵)
Our Question?
Our #SARSCoV2 humanized ACE2 mouse pathogenesis model paper is now out in #PLOSPathogens . Great effort from many and led by my great colleague Bev Koller.
We find that hACE2 expression is regulated by upstream and intragenic elements.
Author summary SARS-CoV-2, the virus responsible for COVID-19, infects the human respiratory tract by binding to angiotensin-converting enzyme 2 (ACE2), a protein on the outer surface of cells that is exposed to the air we inhale. Differences in the structure of ACE2 between mouse and man prevent the virus from infecting cells lining the airways of the mouse, limiting the usefulness of wildtype mice as a model system for studying COVID-19. To circumvent this problem, we have created two mouse lines in which the chromosomal segment that encodes the mouse ACE2 protein has been replaced with the equivalent segment of human DNA. In the first of these lines, expression of human ACE2 is regulated by the mouse upstream promoter, while in the second line it is regulated by the human upstream promoter. Using these mice, we show both qualitative and quantitative differences between ACE2 expression driven by the mouse and human promoters that are likely to impact disease progression in the two species. Mice expressing the full-length human ACE2 gene under the control of its own promoter should provide a useful model system for understanding the complex pathological processes and immune responses associated with COVID-19 in humans.
Author summary Transposable elements (TEs) are engines of evolution over short and long evolutionary time scales and have played crucial roles in pathogen evolution. The impacts of TEs are multifaceted, ranging from creating adaptive sequence variants, gene disruptions, chromosomal rearrangements or even triggers of genome expansions. As a defense, pathogen genomes have evolved sophisticated mechanisms to silence or mutate TEs. Pathogens have also benefited from TEs thanks to altered virulence genes and increased antifungal resistance. How TEs cope with genomic defenses and expand in genomes (i.e., cause TE bursts) remains poorly understood though. We analyzed over a dozen high-quality genomes of a fungal wheat pathogen species, which has recently experienced TE reactivations. We reconstructed the evolutionary history of many TEs by building phylogenetic trees. Using this approach, we identified "invasion routes", i.e., tracking TE copies that constitute the most likely ancestors of renewed activity of TEs (i.e. a bursts). Our work showed that specific features, in particular the proximity to genes, were likely important drivers leading the reactivation of TEs.
Author summary Seasonal influenza, especially for A(H3N2), has a considerable impact on public health around the world. Until now, quantitatively characterizing the underlying mechanism for the circulation of influenza A(H3N2) remains challenging, especially for countries with diverse seasonal patterns. China is a climatologically diverse country, where the seasonal pattern of influenza A(H3N2) varies across regions. Using multi-source data, the mechanism for the heterogenic transmission patterns of influenza A(H3N2) in China was revealed through an integrative modelling framework. The contributions of population susceptibility, climate factors and antigenic change to the dynamics of influenza A(H3N2) were also quantified. Finally, the effects of interventions on the summer epidemics were tested to help for optimizing the routine influenza immunization campaigns in China. The quantitative understanding of the interplay among driving factors on the circulation of influenza A(H3N2) highlights the importance of simultaneous monitoring of fluctuations for related factors, which is crucial for precise and targeted prevention and control of seasonal influenza.
Animal models for long Covid, review at #PlosPathogens
"We review SARS-CoV-2 infection and disease manifestations in mice, Syrian hamsters, ferrets, and nonhuman primates (NHPs). Specifically, the virology, pathology, immune responses, and multiorgan involvement are summarized. These models are rationally examined for their use in understanding the complexities of the multiorgan involvement during Long COVID and the potential for their use in screening therapeutics such as anti-inflammatory drugs, which are currently used for treating other diseases. The aim of this review is to highlight Long COVID preclinical animal models that could be used for Long COVID research and to screen for pharmacological interventions."
#Covid19 #LongCovid #Covid #SarsCoV2
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010741
Author summary Not everyone who develops COVID-19 (Coronavirus Disease 2019) recovers completely after 5 days, 14 days, or even 12 weeks. People who experience continuing or new symptoms such as fatigue, difficulty breathing, joint pain, heart dysfunction, and memory issues are now recognized as having “Long COVID” or Post-Acute Sequelae of COVID-19 (PASC). Although Long COVID has been estimated to affect 30% to 75% of recovering COVID-19 patients in some studies, the illness is poorly understood, leaving us unable to properly support patients in their recovery. Here, we summarize COVID-19 and Long COVID in people then discuss the potential utility of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) animal models to address problems of Long COVID. We review SARS-CoV-2 infection and disease manifestations in mice, Syrian hamsters, ferrets, and nonhuman primates (NHPs). Specifically, the virology, pathology, immune responses, and multiorgan involvement are summarized. These models are rationally examined for their use in understanding the complexities of the multiorgan involvement during Long COVID and the potential for their use in screening therapeutics such as anti-inflammatory drugs, which are currently used for treating other diseases. The aim of this review is to highlight Long COVID preclinical animal models that could be used for Long COVID research and to screen for pharmacological interventions.
DaveFinlayTCD
David R. Martinez
Clément Goubert 
SenPei
Thiago Carvalho