Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.
We show here that, whilst MDCK cells are resistant to adenovirus infection and hence appear functionally CAR-deficient, polarized MDCK cells express significant levels of CAR sequestered on the basolateral surface, where it is inaccessible for virus infection.
Additionally, the level of cellular glycogen synthase kinase 3β (GSK3β) is downregulated by SSS exposure and treatment with a specific GSK3β inhibitor recapitulates the effects of SSS exposure on CAR expression and viral infection.
In polarized epithelia, a low-abundance, alternatively spliced eight-exon isoform of CAR, CAR(Ex8), is localized apically where it can support viral infection from the air-exposed surface.
Recent data indicate that the up-regulation of coxsackievirus and adenovirus receptor (CAR) in viral cardiomyopathy contributes to viral infection as a key factor in the pathogenesis of this disease.
Low hCAR abundance may render normal human myocardium resistant to CAR-dependent viruses, whereas re-expression of hCAR, such as that observed in DCM, may be a key determinant of cardiac susceptibility to viral infections.