Reovirus sigma1 fiber incorporated into adenovirus serotype 5 enhances infectivity via a CAR-independent pathway.
Adenovirus serotype 5 (Ad5) has been used for gene therapy with limited success because of insufficient infectivity in cells with low expression of the primary receptor, the coxsackie and adenovirus receptor (CAR). To enhance infectivity in tissues with low CAR expression, tropism expansion is required via non-CAR pathways. Serotype 3 Dearing reovirus utilizes a fiber-like sigma1 protein to infect cells expressing sialic acid and junction adhesion molecule 1 (JAM1). We hypothesized that replacement of the Ad5 fiber with sigma1 would result in an Ad5 vector with CAR-independent tropism. We therefore constructed a fiber mosaic Ad5 vector, designated as Ad5-sigma1, encoding two fibers: the sigma1 and the wild-type Ad5 fiber. Functionally, Ad5-sigma1 utilized CAR, sialic acid, and JAM1 for cell transduction and achieved maximum infectivity enhancement in cells with or without CAR. Thus, we have developed a new type of Ad5 vector with expanded tropism, possessing fibers from Ad5 and reovirus, that exhibits enhanced infectivity via CAR-independent pathway(s).
Tsuruta
Yuko
Y
Division of Human Gene Therapy, Department of Medicine, and The Gene Therapy Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Pereboeva
Larisa
L
Glasgow
Joel N
JN
Luongo
Cindy L
CL
Komarova
Svetlana
S
Kawakami
Yosuke
Y
Curiel
David T
DT
D000256:Adenoviridae / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D011991:Receptors, Virus / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012087:Reoviridae / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D015815:Cell Adhesion Molecules; C407243:F11R protein, human; C498686:F11r protein, mouse; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C085301:adenovirus receptor; D019158:N-Acetylneuraminic Acid