Human hepatocyte growth factor receptor is a cellular coreceptor for adeno-associated virus serotype 3.
Adeno-associated viruses (AAVs) use a variety of cellular receptors/coreceptors to gain entry into cells. A number of AAV serotypes are now available, and the cognate receptors/coreceptors for only a handful of those have been identified thus far. Of the 10 commonly used AAV serotypes, AAV3 is by far the least efficient in transducing cells in general. However, in our more recent studies, we observed that AAV3 vectors transduced human liver cancer cells remarkably well, which led to the hypothesis that AAV3 uses hepatocyte growth factor receptor (HGFR) as a cellular coreceptor for viral entry. AAV3 infection of human liver cancer cell lines was strongly inhibited by hepatocyte growth factor, HGFR-specific small interfering RNA, and anti-HGFR antibody, which corroborated this hypothesis. However, AAV3 vectors failed to transduce murine hepatocytes, both in vitro and in vivo, suggesting that AAV3 specifically uses human HGFR, but not murine HGFR, as a cellular coreceptor for transduction. AAV3 may prove to be a useful vector for targeting human liver cancers for the potential gene therapy.
Ling
Chen
C
Department of Pediatrics, University of Florida College of Medicine, Gainesville, 32611, USA.
Lu
Yuan
Y
Kalsi
Jasmine K
JK
Jayandharan
Giridhara R
GR
Li
Baozheng
B
Ma
Wenqin
W
Cheng
Binbin
B
Gee
Samantha W Y
SW
McGoogan
Katherine E
KE
Govindasamy
Lakshmanan
L
Zhong
Li
L
Agbandje-McKenna
Mavis
M
Srivastava
Arun
A
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017434:Protein Structure, Tertiary; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D056189:Viral Tropism; D053586:Virus Internalization
D017978:Receptors, Growth Factor; D011991:Receptors, Virus; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met