Adenovirus Biology, Recombinant Adenovirus, and Adenovirus Usage in Gene Therapy.

Gene therapy is currently in the public spotlight. Several gene therapy products, including oncolytic virus (OV), which predominantly replicates in and kills cancer cells, and COVID-19 vaccines have recently been commercialized. Recombinant adenoviruses, including replication-defective adenoviral vector and conditionally replicating adenovirus (CRA; oncolytic adenovirus), have been extensively studied and used in clinical trials for cancer and vaccines. Here, we review the biology of wild-type adenoviruses, the methodological principle for constructing recombinant adenoviruses, therapeutic applications of recombinant adenoviruses, and new technologies in pluripotent stem cell (PSC)-based regenerative medicine. Moreover, this article describes the technology platform for efficient construction of diverse "CRAs that can specifically target tumors with multiple factors" (m-CRAs). This technology allows for modification of four parts in the adenoviral E1 region and the subsequent insertion of a therapeutic gene and promoter to enhance cancer-specific viral replication (i.e., safety) as well as therapeutic effects. The screening study using the m-CRA technology successfully identified survivin-responsive m-CRA (Surv.m-CRA) as among the best m-CRAs, and clinical trials of Surv.m-CRA are underway for patients with cancer. This article also describes new recombinant adenovirus-based technologies for solving issues in PSC-based regenerative medicine.

Tree Shrew as an Emerging Small Animal Model for Human Viral Infection: A Recent Overview.

Viral infection is a global public health threat causing millions of deaths. A suitable small animal model is essential for viral pathogenesis and host response studies that could be used in antiviral and vaccine development. The tree shrew (Tupaia belangeri or Tupaia belangeri chinenesis), a squirrel-like non-primate small mammal in the Tupaiidae family, has been reported to be susceptible to important human viral pathogens, including hepatitis viruses (e.g., HBV, HCV), respiratory viruses (influenza viruses, SARS-CoV-2, human adenovirus B), arboviruses (Zika virus and dengue virus), and other viruses (e.g., herpes simplex virus, etc.). The pathogenesis of these viruses is not fully understood due to the lack of an economically feasible suitable small animal model mimicking natural infection of human diseases. The tree shrew model significantly contributes towards a better understanding of the infection and pathogenesis of these important human pathogens, highlighting its potential to be used as a viable viral infection model of human viruses. Therefore, in this review, we summarize updates regarding human viral infection in the tree shrew model, which highlights the potential of the tree shrew to be utilized for human viral infection and pathogenesis studies.

Human Coronavirus NL63 Among Other Respiratory Viruses in Clinical Specimens of Egyptian Children and Raw Sewage Samples.

The objective of this study was to investigate human coronavirus NL63 (HCoV-NL63) prevalence among the other respiratory viruses such as parainfluenza, respiratory syncytial virus, and non-enteric adenoviruses in clinical specimens of Egyptian children and raw sewage samples. One hundred clinical specimens were collected from Egyptian children suffering from upper and lower respiratory viral infections in the years 2005-2006 to detect HCoV-NL63 genome using RT-PCR. All the specimens were negative for the virus. Also, a complete absence of HCoV-NL63 genome was observed in the twenty-four raw sewage samples collected from two wastewater treatment plants within Greater Cairo from February 2006 to January 2007. Using nested RT-PCR, parainfluenza virus type 1, respiratory syncytial virus type A, adenovirus type 4, and adenovirus type 7 were detected in 3%, 2%, 5%, and 2% of the clinical specimens, respectively. Of these viruses, only adenovirus type 4 was detected in 1/24 (4.17%) of the raw sewage samples, while a complete absence of the other investigated respiratory viruses was observed in the raw sewage samples. The low percentage of positivity in the clinical specimens, the concentration method of the raw sewage samples, and the indirect routes of transmission may be the reasons for the absence of respiratory viruses in raw sewage samples. On the other hand, enteric adenoviruses were detected in 21/24 (87.5%) of the raw sewage samples with a higher prevalence of adenovirus type 41 than adenovirus type 40. A direct route of transmission of enteric viruses to raw sewage may be the reason for the high positivity percentage of enteric adenoviruses in raw sewage samples.