Modulation of adenoviral transduction in vitro and in vivo by hyaluronan and its receptor CD44.
Adenovirus infection is a significant cause of ocular, respiratory, and gastrointestinal illness and can spread rapidly. Morbidity is considerable in immune-suppressed individuals and there is significant mortality. There are no effective therapies. During preclinical studies of adenoviral-mediated gene therapy for ocular disorders, we noticed a significant increase in transduction when the target cells were exposed to adenovirus in the presence of ocular vitreous. The vitreous is mainly comprised of water, collagen, and the large polysaccharide hyaluronan. In this paper, we report data that implicate hyaluronan in the adenoviral infectious process and show that interference with the interaction between hyaluronan and its cellular receptor CD44 can block adenovirus transduction in vitro and in vivo.
Chaudhuri
Saumya R
SR
1Department of Pediatrics, Texas Children's Cancer Center and Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
Mallam
Joshua N
JN
Chévez-Barrios
Patricia
P
Wadhwa
Lalita
L
Ng
Philip
P
Hurwitz
Mary Y
MY
Hurwitz
Richard L
RL
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D014161:Transduction, Genetic
D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid