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Abstract Analyzing the impact of the adaptive immune response during acute hepatitis B virus (HBV) infection is essential for understanding disease progression and control. Here we developed mathematical models of HBV infection which either lack terms for adaptive immune responses, or assume adaptive immune responses in the form of cytolytic immune killing, non-cytolytic immune cure, or non-cytolytic-mediated block of viral production. We validated the model that does not include immune responses against temporal serum hepatitis B DNA (sHBV) and temporal serum hepatitis B surface-antigen (HBsAg) experimental data from mice engrafted with human hepatocytes (HEP). Moreover, we validated the immune models against sHBV and HBsAg experimental data from mice engrafted with HEP and human immune system (HEP/HIS). As expected, the model that does not include adaptive immune responses matches the observed high sHBV and HBsAg concentrations in all HEP mice. By contrast, while all immune response models predict reduction in sHBV and HBsAg concentrations in HEP/HIS mice, the Akaike Information Criterion cannot discriminate between non-cytolytic cure (resulting in a class of cells refractory to reinfection) and antiviral block functions (of up to$$99\%$$ viral production 1–3 weeks following peak viral load). We can, however, reject cytolytic killing, as it can only match the sHBV and HBsAg data when we predict unrealistic levels of hepatocyte loss.
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SARS-Cov-2 small viral RNA suppresses gene expression via complementary binding to mRNA 3’ UTR
SARS-CoV-2 (SC2) has been intensely studied since its emergence. However, the mechanisms of host immune dysregulation triggered by SC2 remain poorly understood. That said, it is well established that many prominent viral families encode microRNAs (miRNAs) or related small viral RNAs (svRNAs) capable of regulating human genes involved in immune function. Importantly, recent reports have shown that SC2 encodes its own svRNAs. In this study, we have identified 12 svRNAs expressed during SC2 infection and show that one of these svRNAs can regulate target gene expression via complementary binding to mRNA 3’ untranslated regions (3’UTRs) much like human microRNAs.
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- PAR ID:
- 10613995
- Publisher / Repository:
- microPublication Biology
- Date Published:
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Data Paper:
- https://doi.org/10.17912/micropub.biology.000790
