A novel system to study adenovirus tropism to normal and malignant colon tissues.
We describe here a new organ culture system for the evaluation of viral tropism to colon carcinomas and normal colon tissues. Organ cultures of mouse and human colon retained viability for several days and thus facilitated studies of viral tropism. Two adenoviral vectors (AD) were compared in the study: AD5, that utilizes the CAR receptor, demonstrated poor infectivity to both normal and carcinoma tissues, while a capsid-modified-AD, recognizing haparan-sulfate receptor, demonstrated efficient infectivity of both tissues. Immunohistochemistry analysis demonstrated different viral tropism; while AD5 infected only the colon epithelia, the capsid-modified-adeno infected both the epithelia and mesothelial layers. To investigate other determinants in the tissue that influence viral tropism, human cancer tissues were pretreated with collagenase and infected with the AD viruses. Increased infectivity and altered tropism were noted in the treated tumor tissue. Taken together, this ex vivo system indicated that receptor utilization and extracellular-matrix components influence AD viral tropism in solid tissues.
Kolodkin-Gal
D
D
Department of Virology, The Hebrew University- Hadassah Medical School, The Hebrew University, Jerusalem, 91120, Israel.
Zamir
G
G
Pikarski
E
E
Pikarski
A
A
Shimony
N
N
Wu
H
H
Haviv
Y S
YS
Panet
A
A
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D017498:Adenovirus E1 Proteins / Q000235:genetics; D000818:Animals; D002213:Capsid / Q000378:metabolism; D017364:Collagenases; D003106:Colon / Q000821:virology*; D003110:Colonic Neoplasms / Q000821:virology*; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004848:Epithelium / Q000821:virology; D017353:Gene Deletion; D005822:Genetic Vectors; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental; D009924:Organ Culture Techniques / Q000379:methods*; D011991:Receptors, Virus / Q000378:metabolism; D013045:Species Specificity; D014779:Virus Replication
D017498:Adenovirus E1 Proteins; D017364:Collagenases; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D006497:Heparan Sulfate; D011991:Receptors, Virus; C568771:CLMP protein, human; C568772:CLMP protein, mouse