Practice question

Adenoviral vectors derived from nonenveloped icosahedral dsDNA viruses genome 26-36 kb flanked by inverted terminal repeats and packaging signal possess capacity 8 kb in first-generation deleted E1/E3 and up to 30 kb in helper-dependent gutless vectors lacking all viral coding sequences. Infection initiated by fiber knob binding CAR and alphaV beta3 integrin, internalization via clathrin pits, partial capsid disassembly releasing protein VI that lyses early endosomes at pH 6.0 permitting cytosolic transport via dynein to nuclear pore where genome translocates and remains extrachromosomal as linear and circular episome associated with histones without integrase. Expression from strong CMV promoter peaks 24-48 hours achieving high mRNA levels but declines over weeks in dividing tissue due to episomal loss and promoter methylation. Capsid hexon and fiber trigger innate immunity via TLR2, TLR9, NLRP3 inflammasome producing IL-6 and IL-1 beta and adaptive CTL response clearing transduced cells within two weeks. Transient high-level nonintegrating profile favors oncolytic therapy, vaccine delivery, and provision genome-editing enzymes.