Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection

Introduction: Recombination-activating gene 1 (Rag1) and Rag2, which are essential in V(D)J recombination, play a crucial role in B and T cell maturation. Method: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. Results: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including MIP-1α, IP-10, IFN-α, IFN-γ, and TNF-α, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. Conclusion: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases.

Real-World Single-Center Comparison of the Safety and Efficacy of Entecavir, Tenofovir Disoproxil Fumarate, and Tenofovir Alafenamide in Patients with Chronic Hepatitis B

<b><i>Introduction:</i></b> Chronic hepatitis B (CHB) is a major cause of chronic liver diseases and tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir (ETV) are recommended as primary treatments. This study aimed to evaluate the efficacy and safety of ETV, TDF, and TAF in a real-world clinical setting. <b><i>Methods:</i></b> In this retrospective cohort study, a total of 363 CHB patients who were treated with ETV (<i>n</i> = 163), TDF (<i>n</i> = 154), or TAF (<i>n</i> = 46) from July 2007 to September 2019 were enrolled. <b><i>Results:</i></b> Median patient age was 51 years and 66.4% of patients were male. Median duration of treatment with ETV, TDF, or TAF was 49.0 months (interquartile range, 27.0–74.0 months). In terms of safety, cholesterol was mildly increased in the ETV and TAF groups and significantly lowered in the TDF group than baseline (<i>p</i> &#x3c; 0.001). There was no significant difference in liver cirrhosis-related complications among the 3 groups at 48 weeks (<i>p</i> = 0.235). Hepatitis B e antigen seroconversion, complete virological response, and alanine aminotransferase normalization at 48 weeks as measures of treatment efficacy were not significantly different among the 3 groups (<i>p</i> = 0.142, 0.538, and 0.520, respectively). There was also no significant difference in cumulative incidence rate of hepatocellular carcinoma (HCC) between the ETV and TDF groups (<i>p</i> = 0.894). <b><i>Conclusions:</i></b> ETV, TDF, and TAF were safe antiviral agents and showed similar antiviral effect for CHB at 48 weeks. Cirrhosis-related complications and annual HCC incidence rates did not differ significantly between the ETV and TDF groups over the 48 week follow-up period.

Molecular detection of parvovirus in Manchurian chipmunks (Tamias sibiricus asiaticus) captured in Korea

Cross-species transmission of viral diseases alarms our global community for its potential of novel pandemic events. Of various viral pathogens noted recently, parvoviruses have posed public health threats not only to humans but to wild animals. To investigate the prevalence of parvoviruses in wild Manchurian chipmunks, here we detected genetic fragments of the nonstructural protein of parvovirus by polymerase chain reaction in wild Manchurian chipmunk specimens captured in the central and southern regions of South Korea and compared their sequence homology with references. Of a total of 348 specimens examined, chipmunk parvovirus (ChpPV)-specific gene fragments were detected with a 31.32 % rate (109 chipmunks of 348) in their kidney, liver, lung, and spleen samples, and the chipmunks captured in Gangwon Province exhibited the highest positive rate (45.37%), followed by Gyeongsang (35.29%), Gyeonggi (31.03%), Chungcheong (20.00%), and Jeolla (19.70%). When compared with the reference sequences registered in GenBank, a partial ChpPV sequence showed 97.70% identity to the previously reported Korean strain at the nucleic acid level. In the phylogenetic analysis, ChpPV exhibited closer relationship to primate parvoviruses, erythroviruses, and bovine parvovirus than to adeno-associated viruses. Despite limited sample size and genetic sequences examined in this study, our results underline the prevalence of ChpPV in Korea and emphasize the need of close surveillance of parvoviruses in wild animals.

The Features of Pathobiology and Clinical translation of Approved treatments for Coronavirus Disease 2019 (COVID-19)

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently the most important etiological agent of acute respiratory distress syndrome (ARDS) with millions of infections and deaths in the last two years worldwide. Several reasons and parameters are responsible for the difficult management of coronavirus disease-2019 (COVID-19) patients; the first is virus behavioral factors such as high transmission rate, and the different molecular and cellular mechanisms of pathogenesis remain a matter of controversy, is another factor. Summary: In the present review, we attempted to explain about features of SARS-COV-2, particularly focusing on the various aspects of pathogenesis and treatment strategies. Key Messages: We note evidence for the understanding of the precise molecular and cellular mechanisms of SARS-CoV-2 pathogenesis, which can help design the appropriate drug or vaccine. Additionally, and importantly, we reported the updated issues associated with the history and development of treatment strategies such as, drugs, vaccines, and other medications that have been approved or under consideration in clinics and markets worldwide.