Pancreatic acinar and islet cell infection by low-dose SV40 administration.
OBJECTIVE
Viral vector uptake into the pancreas is rare. The few viral vectors reported to transduce in vivo pancreatic islets after systemic injection required additional physical measures, such as direct pancreatic injection or hepatic vessel clamping. Because pancreatic islet uptake of the human polyomavirus family member BK virus was previously reported in hamsters after systemic administration, we hypothesized that SV40, a polyomavirus member remarkably similar to BK virus, may also infect the pancreas.


METHODS
We injected intravenously a low dose of SV40, unaided by any other physical or chemical means, and evaluated viral uptake by pancreatic islets and pancreatic exocrine tissue via polymerase chain reaction, Western blot, electron microscopy, immunofluorescent microscopy, and protein A-gold immunocytochemistry.


RESULTS
Pancreatic uptake of SV40 was comparable to other major organs (ie, liver and spleen). SV40 viral particles were detected in both pancreatic islets and acini. In pancreatic islets, all islet cell types were infected by SV40, albeit the infection rate of glucagon-producing alpha cells surpassed beta- and delta-islet cells. Low-dose SV40 administration was not sufficient to induce heterologous gene expression in the pancreas.


CONCLUSIONS
Our study shows that pancreatic islet and acinar cell uptake of SV40 is feasible with a single, low-dose intravenous injection. However, this dose did not result in gene delivery into the murine pancreas.
Shimony
Nilly
N
Cell and Gene Therapy Program, Division of Nephrology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Bendayan
Moise
M
Elkin
Gregory
G
Ben-nun-Shaul
Orly
O
Abd-El-Latif
Mahmoud
M
Scherzer
Pnina
P
Arbel
Ofer
O
Ziv
Ehud
E
Krasny
Lina
L
Pizov
Galina
G
Oppenheim
Ariella
A
Haviv
Yosef S
YS
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D007515:Islets of Langerhans / Q000648:ultrastructure / Q000821:virology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010182:Pancreatic Diseases / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D013539:Simian virus 40 / Q000302:isolation & purification / Q000472:pathogenicity* / Q000648:ultrastructure